1
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Bomidi C, Sawyer FM, Shroyer N, Conner M, Estes MK, Blutt SE. Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection. J Virol 2025; 99:e0150724. [PMID: 39727412 PMCID: PMC11852729 DOI: 10.1128/jvi.01507-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, based on lack of shedding virus, despite the highly infectious nature of RV. This response was directly proportional to the extent of secretory cell deletion, with infection predominantly occurring in areas containing intact secretory cells. RV infection of Muc2 knockout mice recapitulated the secretory cell deletion phenotype, indicating that goblet cell loss is responsible for attenuated infection. Transcriptome analysis of Atoh1cKO intestine via single-cell RNA sequencing revealed downregulation of MHC II molecules specifically in tip enterocytes, and MHC II-/- mice were likewise resistant to RV infection. These data suggest a previously unknown role for both MUC2 and MHC II expression in susceptibility to RV infection.IMPORTANCERotavirus (RV) is a highly contagious pathogen that primarily infects mature intestinal enterocytes. Murine rotavirus readily infects infant and adult mice, enabling evaluation of RV infection and immunity. We report that mice lacking secretory cells are one of the few genetically modified mouse lines not susceptible to murine rotavirus. Further investigation revealed loss of mucin 2 (MUC2) expression or major histocompatibility complex II (MCH II) expression recapitulated this rare resistance to rotavirus infection, suggesting a previously unrecognized link between secretory cell products and major histocompatibility complex II expression. Furthermore, these mouse models provide a platform to investigate rotavirus pathogenesis.
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Affiliation(s)
- Carolyn Bomidi
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Faith M. Sawyer
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Noah Shroyer
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Margaret Conner
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Mary K. Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Sarah E. Blutt
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
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2
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Wu L, Jing Z, Pan Y, Guo L, Li Z, Feng L, Tian J. Emergence of a novel pathogenic porcine G1P[7] rotavirus in China. Virology 2024; 598:110185. [PMID: 39096775 DOI: 10.1016/j.virol.2024.110185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 07/07/2024] [Accepted: 07/20/2024] [Indexed: 08/05/2024]
Abstract
Among group A rotaviruses (RVAs), the G1 genotype is the main genotype causing diarrhea in children, but it has rarely been reported in pigs. During our epidemiological investigation, we detected G1P[7] rotavirus infection in piglets across several provinces in China and then isolated a porcine G1P[7] rotavirus strain (CN1P7). Sequencing revealed that the virus constellation was G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analyses revealed that CN1P7 most likely emerged due to genetic reassortment among porcine, human, giant panda and dog rotavirus strains. In vivo experiments were conducted on two-day-old piglets, which revealed that the CN1P7 strain was pathogenic to piglets. The virus was shed through the digestive tract and respiratory tract. In addition to the intestine, the CN1P7 strain displayed extraintestinal tropisms in piglets. Histopathological analysis revealed that the lung and small intestine were the targets of CN1P7. This study is the first to explore the molecular and pathogenic characterization of a pig-origin G1P[7] rotavirus.
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Affiliation(s)
- Ling Wu
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
| | - Zhaoyang Jing
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
| | - Yudi Pan
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
| | - Longjun Guo
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
| | - Zixin Li
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China
| | - Li Feng
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
| | - Jin Tian
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
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3
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Chen Q, Chen Y, Bao C, Xiang H, Gao Q, Mao L. Mechanism and complex roles of HSC70/HSPA8 in viral entry. Virus Res 2024; 347:199433. [PMID: 38992806 PMCID: PMC11305274 DOI: 10.1016/j.virusres.2024.199433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/05/2024] [Accepted: 07/06/2024] [Indexed: 07/13/2024]
Abstract
The process of viruses entering host cells is complex, involving multiple aspects of the molecular organization of the cell membrane, viral proteins, the interaction of receptor molecules, and cellular signaling. Most viruses depend on endocytosis for uptake, when viruses reach the appropriate location, they are released from the vesicles, undergo uncoating, and release their genomes. Heat shock cognate protein 70(HSC70): also known as HSPA8, a protein involved in mediating clathrin-mediated endocytosis (CME), is involved in various viral entry processes. In this mini-review, our goal is to provide a summary of the function of HSC70 in viral entry. Understanding the interaction networks of HSC70 with viral proteins helps to provide new directions for targeted therapeutic strategies against viral infections.
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Affiliation(s)
- Qiaoqiao Chen
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, PR China
| | - Yiwen Chen
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, PR China
| | - Chenxuan Bao
- Department of Laboratory Medicine, Affiliated Kunshan Hospital of Jiangsu University,Kunshan, Jiangsu, PR China
| | - Huayuan Xiang
- Department of Laboratory Medicine, Affiliated Kunshan Hospital of Jiangsu University,Kunshan, Jiangsu, PR China
| | - Qing Gao
- Department of Laboratory Medicine, Affiliated Kunshan Hospital of Jiangsu University,Kunshan, Jiangsu, PR China
| | - Lingxiang Mao
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, PR China; Department of Laboratory Medicine, Affiliated Kunshan Hospital of Jiangsu University,Kunshan, Jiangsu, PR China.
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4
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Jalilvand S, Latifi T, Kachooei A, Mirhoseinian M, Hoseini-Fakhr SS, Behnezhad F, Roohvand F, Shoja Z. Circulating rotavirus strains in children with acute gastroenteritis in Iran, 1986 to 2023 and their genetic/antigenic divergence compared to approved vaccines strains (Rotarix, RotaTeq, ROTAVAC, ROTASIIL) before mass vaccination: Clues for vaccination policy makers. Virus Res 2024; 346:199411. [PMID: 38823689 PMCID: PMC11190746 DOI: 10.1016/j.virusres.2024.199411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/18/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
In the present study, first, rotaviruses that caused acute gastroenteritis in children under five years of age during the time before the vaccine was introduced in Iran (1986 to 2023) are reviewed. Subsequently, the antigenic epitopes of the VP7 and VP4/VP8 proteins in circulating rotavirus strains in Iran and that of the vaccine strains were compared and their genetic differences in histo-blood group antigens (HBGAs) and the potential impact on rotavirus infection susceptibility and vaccine efficacy were discussed. Overall data indicate that rotavirus was estimated in about 38.1 % of samples tested. The most common genotypes or combinations were G1 and P[8], or G1P[8]. From 2015 to 2023, there was a decline in the prevalence of G1P[8], with intermittent peaks of genotypes G3P[8] and G9P[8]. The analyses suggested that the monovalent Rotarix vaccine or monovalent vaccines containing the G1P[8] component might be proper in areas with a similar rotavirus genotype pattern and genetic background as the Iranian population where the G1P[8] strain is the most predominant and has the ability to bind to HBGA secretors. While the same concept can be applied to RotaTeq and RotasIIL vaccines, their complex vaccine technology, which involves reassortment, makes them less of a priority. The ROTASIIL vaccine, despite not having the VP4 arm (P[5]) as a suitable protection option, has previously shown the ability to neutralize not only G9-lineage I strains but also other G9-lineages at high titers. Thus, vaccination with the ROTASIIL vaccine may be more effective in Iran compared to RotaTeq. However, considering the rotavirus genotypic pattern, ROTAVAC might not be a good choice for Iran. Overall, the findings of this study provide valuable insights into the prevalence of rotavirus strains and the potential effectiveness of different vaccines in the Iranian and similar populations.
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Affiliation(s)
- Somayeh Jalilvand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Tayebeh Latifi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Atefeh Kachooei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahtab Mirhoseinian
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Farzane Behnezhad
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farzin Roohvand
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Zabihollah Shoja
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran.
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5
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Raev SA, Kick MK, Chellis M, Amimo JO, Saif LJ, Vlasova AN. Histo-Blood Group Antigen-Producing Bacterial Cocktail Reduces Rotavirus A, B, and C Infection and Disease in Gnotobiotic Piglets. Viruses 2024; 16:660. [PMID: 38793542 PMCID: PMC11125826 DOI: 10.3390/v16050660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/17/2024] [Accepted: 04/19/2024] [Indexed: 05/26/2024] Open
Abstract
The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA- like substances (HBGA+) capable of binding RV particles in vitro. We hypothesized that HBGA+ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA+ or HBGA- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA+ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA+ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA+ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.
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Affiliation(s)
- Sergei A. Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; (S.A.R.); (M.K.K.); (M.C.); (L.J.S.)
| | - Maryssa K. Kick
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; (S.A.R.); (M.K.K.); (M.C.); (L.J.S.)
| | - Maria Chellis
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; (S.A.R.); (M.K.K.); (M.C.); (L.J.S.)
| | | | - Linda J. Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; (S.A.R.); (M.K.K.); (M.C.); (L.J.S.)
| | - Anastasia N. Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; (S.A.R.); (M.K.K.); (M.C.); (L.J.S.)
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6
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Fukuda Y, Kusuhara H, Takai-Todaka R, Haga K, Katayama K, Tsugawa T. Human transmission and outbreaks of feline-like G6 rotavirus revealed with whole-genome analysis of G6P[9] feline rotavirus. J Med Virol 2024; 96:e29565. [PMID: 38558056 DOI: 10.1002/jmv.29565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/01/2024] [Accepted: 03/12/2024] [Indexed: 04/04/2024]
Abstract
Group A rotaviruses (RVAs) are generally highly species-specific; however, some strains infect across species. Feline RVAs sporadically infect humans, causing gastroenteritis. In 2012 and 2013, rectal swab samples were collected from 61 asymptomatic shelter cats at a public health center in Mie Prefecture, Japan, to investigate the presence of RVA and any association with human infections. The analysis identified G6P[9] strains in three cats and G3P[9] strains in two cats, although no feline RVA sequence data were available for the former. A whole-genome analysis of these G6P[9] strains identified the genotype constellation G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3. The nucleotide identity among these G6P[9] strains exceeded 99.5% across all 11 gene segments, indicating the circulation of this G6P[9] strain among cats. Notably, strain RVA/Human-wt/JPN/KF17/2010/G6P[9], previously detected in a 3-year-old child with gastroenteritis, shares high nucleotide identity (>98%) with Mie20120017f, the representative G6P[9] strain in this study, across all 11 gene segments, confirming feline RVA infection and symptomatic presentation in this child. The VP7 gene of strain Mie20120017f also shares high nucleotide identity with other sporadically reported G6 RVA strains in humans. This suggests that feline-origin G6 strains as the probable source of these sporadic G6 RVA strains causing gastroenteritis in humans globally. Moreover, a feline-like human G6P[8] strain circulating in Brazil in 2022 was identified, emphasizing the importance of ongoing surveillance to monitor potential global human outbreaks of RVA.
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Affiliation(s)
- Yuya Fukuda
- Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan
- Laboratory of Viral Infection, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan
| | - Hajime Kusuhara
- Mie Prefecture Health and Environment Research Institute, Mie, Japan
| | - Reiko Takai-Todaka
- Laboratory of Viral Infection, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan
| | - Kei Haga
- Laboratory of Viral Infection, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan
| | - Kazuhiko Katayama
- Laboratory of Viral Infection, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan
| | - Takeshi Tsugawa
- Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan
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7
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Xia M, Huang P, Vago F, Kawagishi T, Ding S, Greenberg HB, Jiang W, Tan M. A Viral Protein 4-Based Trivalent Nanoparticle Vaccine Elicited High and Broad Immune Responses and Protective Immunity against the Predominant Rotaviruses. ACS NANO 2024; 18:6673-6689. [PMID: 38353701 DOI: 10.1021/acsnano.4c00544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
The current live rotavirus (RV) vaccines show reduced effectiveness in developing countries, calling for vaccine strategies with improved efficacy and safety. We generated pseudovirus nanoparticles (PVNPs) that display multiple ectodomains of RV viral protein 4 (VP4), named S-VP4e, as a nonreplicating RV vaccine candidate. The RV spike protein VP4s that bind host receptors and facilitate viral entry are excellent targets for vaccination. In this study, we developed scalable methods to produce three S-VP4e PVNPs, each displaying the VP4e antigens from one of the three predominant P[8], P[4], and P[6] human RVs (HRVs). These PVNPs were recognized by selected neutralizing VP4-specific monoclonal antibodies, bound glycan receptors, attached to permissive HT-29 cells, and underwent cleavage by trypsin between VP8* and VP5*. 3D PVNP models were constructed to understand their structural features. A trivalent PVNP vaccine containing the three S-VP4e PVNPs elicited high and well-balanced VP4e-specific antibody titers in mice directed against the three predominant HRV P types. The resulting antisera neutralized the three HRV prototypes at high titers; greater than 4-fold higher than the neutralizing responses induced by a trivalent vaccine consisting of the S60-VP8* PVNPs. Finally, the trivalent S-VP4e PVNP vaccine provided 90-100% protection against diarrhea caused by HRV challenge. Our data supports the trivalent S-VP4e PVNPs as a promising nonreplicating HRV vaccine candidate for parenteral delivery to circumvent the suboptimal immunization issues of all present live HRV vaccines. The established PVNP-permissive cell and PVNP-glycan binding assays will be instrumental for further investigating HRV-host cell interactions and neutralizing effects of VP4-specific antibodies and antivirals.
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Affiliation(s)
- Ming Xia
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States
| | - Frank Vago
- Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, United States
| | - Takahiro Kawagishi
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States
| | - Siyuan Ding
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States
| | - Harry B Greenberg
- Departments of Medicine and Microbiology and Immunology Emeritus, Stanford University School of Medicine, Stanford, California 94305, United States
| | - Wen Jiang
- Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, United States
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, United States
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8
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Latifi T, Jalilvand S, Golsaz-Shirazi F, Arashkia A, Kachooei A, Afchangi A, Zafarian S, Roohvand F, Shoja Z. Characterization and immunogenicity of a novel chimeric hepatitis B core-virus like particles (cVLPs) carrying rotavirus VP8*protein in mice model. Virology 2023; 588:109903. [PMID: 37832344 DOI: 10.1016/j.virol.2023.109903] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/23/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023]
Abstract
Given the efficacy and safety issues of the WHO for approved/prequalified live attenuated rotavirus (RV) vaccines, studies on alternative non-replicating modals and proper RV antigens are actively undertaken. Herein, we report the novel chimeric hepatitis B core-virus like particles (VLPs) carrying RV VP8*26-231 protein of a P [8] strain (cVLPVP8*), as a parenteral VLP RV vaccine candidate. SDS-PAGE and Western blotting analyses indicated the expected size of the E. coli-derived HBc-VP8* protein that self-assembled to cVLPVP8* particles. Immunization in mice indicated development of higher levels of IgG and IgA as well as higher IgG1/IgG2a ratios by cVLPVP8* vaccination compared to the VP8* alone. Assessment of neutralizing antibodies (nAbs) indicated development of heterotypic nAbs with cross-reactivity to a heterotypic RV strain by cVLPVP8* immunization compared to VP8* alone. The observed anti-VP8* cross-reactivity might indicate the possibility of developing a Pan-genomic RVA vaccine based on the cVLPVP8* formulation that deserves further challenge studies.
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Affiliation(s)
- Tayebeh Latifi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Somayeh Jalilvand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Forough Golsaz-Shirazi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Arashkia
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Atefeh Kachooei
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Atefeh Afchangi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Saman Zafarian
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Department of Microbial Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Farzin Roohvand
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Zabihollah Shoja
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran.
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9
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Poddar S, Roy R, Kar P. Elucidating the conformational dynamics of histo-blood group antigens and their interactions with the rotavirus spike protein through computational lens. J Biomol Struct Dyn 2023; 42:13201-13215. [PMID: 37909470 DOI: 10.1080/07391102.2023.2274979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/18/2023] [Indexed: 11/03/2023]
Abstract
In the present study, we investigated the conformational dynamics of histo-blood group antigens (HBGAs) and their interactions with the VP8* domain of four rotavirus genotypes (P[4], P[6], P[19], and P[11]) utilizing all-atom molecular dynamics simulations in explicit water. Our study revealed distinct changes in the dynamic behavior of the same glycan due to linkage variations. We observed that LNFPI HBGA having a terminal β linkage shows two dominant conformations after complexation, whereas only one was obtained for LNFPI with a terminal α linkage. Interestingly, both variants displayed a single dominant structure in the free state. Similarly, LNT and LNnT show a shift in their dihedral linkage profile between their two terminal monosaccharides because of a change in the linkage from β(1-3) to β(1-4). The molecular mechanics generalized Born surface area (MM/GBSA) calculations yielded the highest binding affinity for LNFPI(β)/P[6] (-13.93 kcal/mol) due to the formation of numerous hydrogen bonds between VP8* and HBGAs. LNnT binds more strongly to P[11] (-12.88 kcal/mol) than LNT (-4.41 kcal/mol), suggesting a single change in the glycan linkage might impact its binding profile significantly. We have also identified critical amino acids and monosaccharides (Gal and GlcNAc) that contributed significantly to the protein-ligand binding through the per-residue decomposition of binding free energy. Moreover, we found that the interaction between the same glycan and different protein receptors within the same rotavirus genogroup influenced the micro-level dynamics of the glycan. Overall, our study helps a deeper understanding of the H-type HBGA and rotavirus spike protein interaction.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Sayan Poddar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Rajarshi Roy
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Parimal Kar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
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10
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Chauwa A, Bosomprah S, Laban NM, Phiri B, Chibuye M, Chilyabanyama ON, Munsaka S, Simuyandi M, Mwape I, Mubanga C, Chobe MC, Chisenga C, Chilengi R. Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix TM) Immunogenicity among Infants in Zambia. Vaccines (Basel) 2023; 11:1303. [PMID: 37631871 PMCID: PMC10458424 DOI: 10.3390/vaccines11081303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/12/2023] [Accepted: 07/24/2023] [Indexed: 08/27/2023] Open
Abstract
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother-infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children.
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Affiliation(s)
- Adriace Chauwa
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
- Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia;
| | - Samuel Bosomprah
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
- Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana
| | - Natasha Makabilo Laban
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
| | - Bernard Phiri
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Mwelwa Chibuye
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
- Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands
| | - Obvious Nchimunya Chilyabanyama
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Sody Munsaka
- Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia;
| | - Michelo Simuyandi
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Innocent Mwape
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Cynthia Mubanga
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Masuzyo Chirwa Chobe
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Caroline Chisenga
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
| | - Roma Chilengi
- Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; (S.B.); (N.M.L.); (B.P.); (M.C.); (O.N.C.); (M.S.); (I.M.); (C.M.); (M.C.C.); (C.C.); (R.C.)
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11
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Lagan P, Mooney MH, Lemon K. Genome analyses of species A rotavirus isolated from various mammalian hosts in Northern Ireland during 2013-2016. Virus Evol 2023; 9:vead039. [PMID: 37547380 PMCID: PMC10403756 DOI: 10.1093/ve/vead039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 05/25/2023] [Accepted: 06/27/2023] [Indexed: 08/08/2023] Open
Abstract
Rotavirus group A (RVA) is the most important cause of acute diarrhoea and severe dehydration in young mammals. Infection in livestock is associated with significant mortality and economic losses and, together with wildlife reservoirs, acts as a potential source of zoonotic transmission. Therefore, molecular surveillance of circulating RVA strains in animal species is necessary to assess the risks posed to humans and their livestock. An RVA molecular epidemiological surveillance study on clinically diseased livestock species revealed high prevalence in cattle and pigs (31 per cent and 18 per cent, respectively) with significant phylogenetic diversity including a novel and divergent ovine artiodactyl DS-1-like constellation G10-P[15]-I2-R2-C2-M2-A11-N2-T6-E2-H3. An RVA gene reassortment occurred in an RVA asymptomatic pig and identified as a G5-P[13] strain, and a non-structural protein (NSP)2 gene had intergenomically reassorted with a human RVA strain (reverse zoonosis) and possessed a novel NSP4 enterotoxin E9 which may relate to the asymptomatic RVA infection. Analysis of a novel sheep G10-P[15] strain viral protein 4 gene imparts a putative homologous intergenic and interspecies recombination event, subsequently creating the new P[15] divergent lineage. While surveillance across a wider range of wildlife and exotic species identified generally negative or low prevalence, a novel RVA interspecies transmission in a non-indigenous pudu deer (zoo origin) with the constellation of G6-P[11]12-R2-C2-M2-A3-N2-T6-E2-H3 was detected at a viral load of 11.1 log10 copies/gram. The detection of novel emerging strains, interspecies reassortment, interspecies infection, and recombination of RVA circulating in animal livestock and wildlife reservoirs is of paramount importance to the RVA epidemiology and evolution for the One Health approach and post-human vaccine introduction era where highly virulent animal RVA genotypes have the potential to be zoonotically transmitted.
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Affiliation(s)
- Paula Lagan
- Virology, Veterinary Science Division, Agri-Food and Biosciences Institute, Stormont, Belfast BT4 3SD, UK
- Institute for Global Food Security, School of Biological Sciences, Queen’s University Belfast BT9 5DL, UK
| | - Mark H Mooney
- Institute for Global Food Security, School of Biological Sciences, Queen’s University Belfast BT9 5DL, UK
| | - Ken Lemon
- Virology, Veterinary Science Division, Agri-Food and Biosciences Institute, Stormont, Belfast BT4 3SD, UK
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12
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Hensley C, Nyblade C, Zhou P, Parreño V, Ramesh A, Frazier A, Frazier M, Garrison S, Fantasia-Davis A, Cai R, Huang PW, Xia M, Tan M, Yuan L. Combined Live Oral Priming and Intramuscular Boosting Regimen with Rotarix ® and a Nanoparticle-Based Trivalent Rotavirus Vaccine Evaluated in Gnotobiotic Pig Models of G4P[6] and G1P[8] Human Rotavirus Infection. Vaccines (Basel) 2023; 11:927. [PMID: 37243031 PMCID: PMC10223133 DOI: 10.3390/vaccines11050927] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/17/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023] Open
Abstract
Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime-boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime-boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime-boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime-boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.
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Affiliation(s)
- Casey Hensley
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Charlotte Nyblade
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Peng Zhou
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Viviana Parreño
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
- INCUINTA, Instituto de Virología e Innovaciones Tecnológicas (IVIT), Instituto Nacional de Tecnología Agropecuaria (INTA)-CONICET, Buenos Aires C1033AAE, Argentina
| | - Ashwin Ramesh
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Annie Frazier
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Maggie Frazier
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Sarah Garrison
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Ariana Fantasia-Davis
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Ruiqing Cai
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
| | - Peng-Wei Huang
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Ming Xia
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Lijuan Yuan
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
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13
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Isolation and Characterization of Distinct Rotavirus A in Bat and Rodent Hosts. J Virol 2023; 97:e0145522. [PMID: 36633410 PMCID: PMC9888233 DOI: 10.1128/jvi.01455-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Rotavirus A (RVA) causes diarrheal disease in humans and various animals. Recent studies have identified bat and rodent RVAs with evidence of zoonotic transmission and genome reassortment. However, the virological properties of bat and rodent RVAs with currently identified genotypes still need to be better clarified. Here, we performed virus isolation-based screening for RVA in animal specimens and isolated RVAs (representative strains: 16-06 and MpR12) from Egyptian fruit bat and Natal multimammate mouse collected in Zambia. Whole-genome sequencing and phylogenetic analysis revealed that the genotypes of bat RVA 16-06 were identical to that of RVA BATp39 strain from the Kenyan fruit bat, which has not yet been characterized. Moreover, all segments of rodent RVA MpR12 were highly divergent and assigned to novel genotypes, but RVA MpR12 was phylogenetically closer to bat RVAs than to other rodent RVAs, indicating a unique evolutionary history. We further investigated the virological properties of the isolated RVAs. In brief, we found that 16-06 entered cells by binding to sialic acids on the cell surface, while MpR12 entered in a sialic acid-independent manner. Experimental inoculation of suckling mice with 16-06 and MpR12 revealed that these RVAs are causative agents of diarrhea. Moreover, 16-06 and MpR12 demonstrated an ability to infect and replicate in a 3D-reconstructed primary human intestinal epithelium with comparable efficiency to the human RVA. Taken together, our results detail the unique genetic and virological features of bat and rodent RVAs and demonstrate the need for further investigation of their zoonotic potential. IMPORTANCE Recent advances in nucleotide sequence detection methods have enabled the detection of RVA genomes from various animals. These studies have discovered multiple divergent RVAs and have resulted in proposals for the genetic classification of novel genotypes. However, most of these RVAs have been identified via dsRNA viral genomes and not from infectious viruses, and their virological properties, such as cell/host tropisms, transmissibility, and pathogenicity, are unclear and remain to be clarified. Here, we successfully isolated RVAs with novel genome constellations from three bats and one rodent in Zambia. In addition to whole-genome sequencing, the isolated RVAs were characterized by glycan-binding affinity, pathogenicity in mice, and infectivity to the human gut using a 3D culture of primary intestinal epithelium. Our study reveals the first virological properties of bat and rodent RVAs with high genetic diversity and unique evolutional history and provides basic knowledge to begin estimating the potential of zoonotic transmission.
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14
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Fukuda Y, Araki K, Hara M, Yamashita Y, Adachi S, Honjo S, Togashi A, Hirakawa S, Fukumura S, Yamamoto M, Tsugawa T. Sequence analysis of a feline- and porcine-origin G3P[9] rotavirus A strain in a child with acute gastroenteritis in Japan. Arch Virol 2023; 168:45. [PMID: 36609581 DOI: 10.1007/s00705-022-05685-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 11/03/2022] [Indexed: 01/08/2023]
Abstract
We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.
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Affiliation(s)
- Yuya Fukuda
- Department of Pediatrics, Japan Red Cross Urakawa Hospital, 1-2-1, Chinomi, Higashimachi, Urakawa-chou, Urakawa-gun, Hokkaido, 057-0007, Japan.,Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Kaoru Araki
- Health Care Center, Saga University, 1 Honjo, Saga City, Saga, 840-8502, Japan
| | - Megumi Hara
- Department of Preventive Medicine, Saga University, 1-1, 5-chome, Nabeshima, Saga City, Saga, 849-8501, Japan
| | - Yuji Yamashita
- Yamashita Children's Clinic, 1-2, 3-chome, Urashi, Itoshima, Fukuoka, 819-1112, Japan
| | - Shuhei Adachi
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Saho Honjo
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Atsuo Togashi
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Satoshi Hirakawa
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Shinobu Fukumura
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Masaki Yamamoto
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Takeshi Tsugawa
- Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
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15
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Tate JE, Cortese MM, Offit PA, Parashar UD. Rotavirus Vaccines. PLOTKIN'S VACCINES 2023:1005-1024.e11. [DOI: 10.1016/b978-0-323-79058-1.00053-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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16
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Raev S, Amimo J, Saif L, Vlasova A. Intestinal mucin-type O-glycans: the major players in the host-bacteria-rotavirus interactions. Gut Microbes 2023; 15:2197833. [PMID: 37020288 PMCID: PMC10078158 DOI: 10.1080/19490976.2023.2197833] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/28/2023] [Indexed: 04/07/2023] Open
Abstract
Rotavirus (RV) causes severe diarrhea in young children and animals worldwide. Several glycans terminating in sialic acids (SAs) and histo-blood group antigens (HBGAs) on intestinal epithelial cell (IEC) surface have been recognized to act as attachment sites for RV. IECs are protected by the double layer of mucus of which O-glycans (including HBGAs and SAs) are a major organic component. Luminal mucins, as well as bacterial glycans, can act as decoy molecules removing RV particles from the gut. The composition of the intestinal mucus is regulated by complex O-glycan-specific interactions among the gut microbiota, RV and the host. In this review, we highlight O-glycan-mediated interactions within the intestinal lumen prior to RV attachment to IECs. A better understanding of the role of mucus is essential for the development of alternative therapeutic tools including the use of pre- and probiotics to control RV infection.
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Affiliation(s)
- S.A. Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
| | - J.O. Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - L.J. Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
| | - A.N. Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
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17
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Farahmand M, Latifi T, Kachooei A, Jalilvand S, Shoja Z. Circulating rotavirus P[8]-lineage IV, unlike P[8]-lineage III, significantly related to nonsecretors status in Iranian children. J Med Virol 2023; 95:e28160. [PMID: 36123611 DOI: 10.1002/jmv.28160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/20/2022] [Accepted: 09/14/2022] [Indexed: 01/11/2023]
Abstract
Rotavirus (RV) P[8] strains are responsible for the most of the RV infections globally and are significantly associated with the secretor and Lewis positive status. Among the distinct P[8] lineages, different ligand affinities have been detected which can be linked to differences in secretor status associated histo-blood group antigens (HBGAs). Herein, we report the lineages of P[8] strains and their associated secretor and Lewis antigen phenotypes in Iranian children. The phylogenetic tree and sequence analyses showed that the most common detected RV P[8] strain belonged to P[8]-lineage III (92%) and were significantly associated with secretor and Lewis positive status. In contrast, 8% of P[8] strains clustered into the P[8]-lineage IV and were significantly associated with nonsecretor status, implying that lineage IV tends to infect nonsecretor individuals. Furthermore, protein modeling and amino acid analyses of the VP8* glycan binding site of Iranian P[8]-lineage IV strains indicated two residual substitutions (T184V and N216V/I) compared to the P[8]-lineage III strains that might have affected the glycan affinity among P[8]-lineages IV strains. The corresponding residual changes might permit their continued transmission in nonsecretor children in competition with other P[8]-lineages. Although nonsecretors show natural resistant to P[8] strains, but such residual changes might overcome this natural resistance which in turn might indirectly contribute to the decline in the vaccine efficacy in populations where HBGA polymorphism allows their circulation at high frequency.
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Affiliation(s)
- Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Tayebeh Latifi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Atefeh Kachooei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Somayeh Jalilvand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Zabihollah Shoja
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran.,Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
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18
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Global Infection Rate of Rotavirus C during 1980-2022 and Analysis of Critical Factors in the Host Range Restriction of Virus VP4. Viruses 2022; 14:v14122826. [PMID: 36560830 PMCID: PMC9781963 DOI: 10.3390/v14122826] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Information on rotavirus C (RVC) infection is lacking, partly because the prevalence of RVC among humans and animals worldwide is undefined. Data on the characteristics of the P genotype among RVC strains are also required. We performed systematic searches on the infection rates of RVC since 1980 based on the literature and gene sequences of the PubMed and GenBank databases. A phylogenetic tree of VP4 genes was constructed to evaluate the distribution of the P genotype of RVC from various hosts. The specific mutation motifs in VP8* with P [2]/P [4]/P [5] specificity were analyzed to elucidate their roles in host range restriction. The rate of RVC infection in humans has fallen from 3% before 2009 to 1%, whereas in animals it has risen from 10% to 25%. The P genotype of RVC showed strict host species specificity, and current human RVC infections are exclusively caused by genotype P [2]. In the VP8* hemagglutinin domain of the P [4]/P [5] genotype of swine RVC, specific insertion or deletion were found relative to the human P [2] genotype, and these motifs are a possible critical factor for host range restriction. Our findings highlight the need for further epidemiological surveillance, preventive strategies, and elucidation of the factors involved in the specific host range restriction of RVC-circulating strains.
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19
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The Association between Symptomatic Rotavirus Infection and Histo-Blood Group Antigens in Young Children with Diarrhea in Pretoria, South Africa. Viruses 2022; 14:v14122735. [PMID: 36560739 PMCID: PMC9782691 DOI: 10.3390/v14122735] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Recently, histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors of several viral pathogens. Among rotaviruses, HBGAs interact with the outer viral protein, VP4, which has been identified as a potential susceptibility factor, although the findings are inconsistent throughout populations due to HBGA polymorphisms. We investigated the association between HBGA phenotypes and rotavirus infection in children with acute gastroenteritis in northern Pretoria, South Africa. METHODS Paired diarrheal stool and saliva samples were collected from children aged ≤ 59 months (n = 342) with acute moderate to severe diarrhea, attending two health care facilities. Rotaviruses in the stool samples were detected by commercial EIA and the rotavirus strains were characterized by RT-PCR targeting the outer capsid VP7 (G-type) and VP4 (P-type) antigens for genotyping. Saliva-based ELISAs were performed to determine A, B, H, and Lewis antigens for blood group typing. RESULTS Blood type O was the most common blood group (62.5%) in this population, followed by groups A (26.0%), B (9.3%), and AB (2.2%). The H1-based secretors were common (82.7%) compared to the non-secretors (17.3%), and the Lewis antigen positive phenotypes (Le(a+b+)) were predominant (54.5%). Blood type A children were more likely to be infected by rotavirus (38.8%) than any other blood types. P[4] rotaviruses (21/49; 42.9%) infected only secretor individuals, whereas P[6] rotaviruses (3/49; 6.1%) only infected Le(a-b-), although the numbers were very low. On the contrary, P[8] rotaviruses infected children with a wide range of blood group phenotypes, including Le(a-b-) and non-secretors. CONCLUSIONS Our findings demonstrated that Lewis antigens, or the lack thereof, may serve as susceptibility factors to rotaviral infection by specific VP4 genotypes as observed elsewhere. Potentially, the P[8] strains remain the predominant human VP4 genotype due to their ability to bind to a variety of HBGA phenotypes.
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Raev SA, Omwando AM, Guo Y, Raque MS, Amimo JO, Saif LJ, Vlasova AN. Glycan-mediated interactions between bacteria, rotavirus and the host cells provide an additional mechanism of antiviral defence. Benef Microbes 2022; 13:383-396. [PMID: 36239669 DOI: 10.3920/bm2022.0026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Limited efficacy of rotavirus (RV) vaccines in children in developing countries and in animals remains a significant problem necessitating further search for additional approaches to control RV-associated gastroenteritis. During cell attachment and entry events, RV interacts with cell surface O-glycans including histo-blood group antigens (HBGAs). Besides modulation of the protective immunity against RV, several commensal and probiotic bacteria were shown to express HBGA-like substances suggesting that they may affect RV attachment and entry into the host cells. Moreover, some beneficial bacteria have been shown to possess the ability to bind host HBGAs via sugar specific proteins called lectins. However, limited research has been done to evaluate the effects of HBGA-expressing and/or HBGA-binding bacteria on RV infection. The aim of this study was to investigate the ability of selected commensal and probiotic bacteria to bind different RV strains via HBGAs and to block RV infection of IPEC-J2 cells. Our data indicated that Gram-negative probiotic Escherichia coli Nissle 1917 (E. coli Nissle 1917) and commensal Gram-positive (Streptococcus bovis and Bifidobacterium adolescentis) and Gram-negative (Bacteroides thetaiotaomicron, Clostridium clostridioforme and Escherichia coli G58 (E. coli G58) bacteria of swine origin expressed HBGAs which correlated with their ability to bind group A and C RVs. Additionally, Gram-positive E. coli 1917 and E. coli G58 demonstrated the ability to block RV attachment onto IPEC-J2 cells. Taken together, our results support the hypothesis that physical interactions between RVs and HBGA-expressing beneficial bacteria may limit RV replication.
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Affiliation(s)
- S A Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - A M Omwando
- Department of Public Health, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Nairobi, P.O. Box 29053, 00625 Nairobi, Kenya
| | - Y Guo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - M S Raque
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - J O Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, P.O. Box 29053, 00625 Nairobi, Kenya
| | - L J Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - A N Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
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21
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Guo Y, Raev S, Kick MK, Raque M, Saif LJ, Vlasova AN. Rotavirus C Replication in Porcine Intestinal Enteroids Reveals Roles for Cellular Cholesterol and Sialic Acids. Viruses 2022; 14:v14081825. [PMID: 36016447 PMCID: PMC9416568 DOI: 10.3390/v14081825] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/14/2022] [Accepted: 08/16/2022] [Indexed: 11/25/2022] Open
Abstract
Rotaviruses (RVs) are a significant cause of severe diarrheal illness in infants and young animals, including pigs. Group C rotavirus (RVC) is an emerging pathogen increasingly reported in pigs and humans worldwide, and is currently recognized as the major cause of gastroenteritis in neonatal piglets that results in substantial economic losses to the pork industry. However, little is known about RVC pathogenesis due to the lack of a robust cell culture system, with the exception of the RVC Cowden strain. Here, we evaluated the permissiveness of porcine crypt-derived 3D and 2D intestinal enteroid (PIE) culture systems for RVC infection. Differentiated 3D and 2D PIEs were infected with porcine RVC (PRVC) Cowden G1P[1], PRVC104 G3P[18], and PRVC143 G6P[5] virulent strains, and the virus replication was measured by qRT-PCR. Our results demonstrated that all RVC strains replicated in 2D-PIEs poorly, while 3D-PIEs supported a higher level of replication, suggesting that RVC selectively infects terminally differentiated enterocytes, which were less abundant in the 2D vs. 3D PIE cultures. While cellular receptors for RVC are unknown, target cell surface carbohydrates, including histo-blood-group antigens (HBGAs) and sialic acids (SAs), are believed to play a role in cell attachment/entry. The evaluation of the selective binding of RVCs to different HBGAs revealed that PRVC Cowden G1P[1] replicated to the highest titers in the HBGA-A PIEs, while PRVC104 or PRVC143 achieved the highest titers in the HBGA-H PIEs. Further, contrasting outcomes were observed following sialidase treatment (resulting in terminal SA removal), which significantly enhanced Cowden and RVC143 replication, but inhibited the growth of PRVC104. These observations suggest that different RVC strains may recognize terminal (PRVC104) as well as internal (Cowden and RVC143) SAs on gangliosides. Finally, several cell culture additives, such as diethylaminoethyl (DEAE)-dextran, cholesterol, and bile extract, were tested to establish if they could enhance RVC replication. We observed that only DEAE-dextran significantly enhanced RVC attachment, but it had no effect on RVC replication. Additionally, the depletion of cellular cholesterol by MβCD inhibited Cowden replication, while the restoration of the cellular cholesterol partially reversed the MβCD effects. These results suggest that cellular cholesterol plays an important role in the replication of the PRVC strain tested. Overall, our study has established a novel robust and physiologically relevant system to investigate RVC pathogenesis. We also generated novel, experimentally derived evidence regarding the role of host glycans, DEAE, and cholesterol in RVC replication, which is critical for the development of control strategies.
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Affiliation(s)
- Yusheng Guo
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Sergei Raev
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Maryssa K. Kick
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Molly Raque
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Linda J. Saif
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Anastasia N. Vlasova
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
- Correspondence:
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22
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Ren X, Saleem W, Haes R, Xie J, Theuns S, Nauwynck HJ. Milk lactose protects against porcine group A rotavirus infection. Front Microbiol 2022; 13:989242. [PMID: 36060735 PMCID: PMC9428151 DOI: 10.3389/fmicb.2022.989242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
Rotavirus A (RVA) is an important pathogen causing acute gastroenteritis in animals and humans. Attachment to the host receptor is a crucial step for virus replication. The VP8* domain is the distal terminal region of the RVA spike protein VP4 (expressed by the P gene) and is important for rotavirus binding and infectivity. Recent studies have indicated a role for non-sialylated glycans, including mucin core 2 and histo-blood group antigens (HBGAs), in the infectivity of human and animal group A rotaviruses. In the present study, we determined if porcine rotavirus-derived recombinant VP8* of the endemic strains 14R103 G5P[6], 13R054 G5P[7], 12R010 G4P[13], 12R046 G9P[23], and 12R022 G2P[27] interact with hitherto uncharacterized glycans. We successfully produced five recombinant GST-VP8* proteins of genotype P[6], P[7], P[13], P[23], and P[27]. The hemagglutination assay showed genotypes P[7] and P[23] hemagglutinate porcine and human red blood cells. In an array screen of > 300 glycans, recombinant VP8* of rotavirus genotype P[6], P[7], and P[13] showed specific binding to glycans with a Gal-β-1,4-Glc (β-lactose) motif, which forms the core structure of HBGAs. The specificity of glycan-binding was confirmed through an ELISA-based oligosaccharide binding assay. Further, 13R054 G5P[7] and 12R046 G9P[23] infectivity was significantly reduced by β-lactose in MA104 cells and primary porcine enterocytes. These data suggest that lactose, the main natural sugar in milk, plays an important role in protecting piglets from enteric viral replication and diarrhea.
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Affiliation(s)
- Xiaolei Ren
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- *Correspondence: Xiaolei Ren,
| | - Waqar Saleem
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Robin Haes
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jiexiong Xie
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Sebastiaan Theuns
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- PathoSense BV, Lier, Belgium
| | - Hans J. Nauwynck
- Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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23
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Xia M, Huang P, Tan M. A Pseudovirus Nanoparticle-Based Trivalent Rotavirus Vaccine Candidate Elicits High and Cross P Type Immune Response. Pharmaceutics 2022; 14:1597. [PMID: 36015223 PMCID: PMC9413348 DOI: 10.3390/pharmaceutics14081597] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 12/27/2022] Open
Abstract
Rotavirus infection continues to cause significant morbidity and mortality globally. In this study, we further developed the S60-VP8* pseudovirus nanoparticles (PVNPs) displaying the glycan receptor binding VP8* domains of rotavirus spike proteins as a parenteral vaccine candidate. First, we established a scalable method for the large production of tag-free S60-VP8* PVNPs representing four rotavirus P types, P[8], P[4], P[6], and P[11]. The approach consists of two major steps: selective precipitation of the S-VP8* proteins from bacterial lysates using ammonium sulfate, followed by anion exchange chromatography to further purify the target proteins to a high purity. The purified soluble proteins self-assembled into S60-VP8* PVNPs. Importantly, after intramuscular injections, the trivalent vaccine consisting of three PVNPs covering VP8* antigens of P[8], P[4], and P[6] rotaviruses elicited high and broad immunogenicity in mice toward the three predominant P-type rotaviruses. Specifically, the trivalent vaccine-immunized mouse sera showed (1) high and balanced IgG and IgA antibody titers toward all three VP8* types, (2) high blocking titer against the VP8*-glycan receptor interaction, and (3) high and broad neutralizing titers against replications of all P[8], P[4], and P[6] rotaviruses. Therefore, trivalent S60-VP8* PVNPs are a promising non-replicating, parenteral vaccine candidate against the most prevalent rotaviruses worldwide.
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Affiliation(s)
- Ming Xia
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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24
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Wu H, Li B, Miao Z, Hu L, Zhou L, Lu Y. Codon usage of host-specific P genotypes (VP4) in group A rotavirus. BMC Genomics 2022; 23:518. [PMID: 35842571 PMCID: PMC9288207 DOI: 10.1186/s12864-022-08730-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/30/2022] [Indexed: 11/26/2022] Open
Abstract
Background Group A rotavirus (RVA) is a common causative agent of acute gastroenteritis in infants and young children worldwide. RVA P genotypes, determined by VP4 sequences, have been confirmed to infect humans and animals. However, their codon usage patterns that are essential to obtain insights into the viral evolution, host adaptability, and genetic characterization remained unclear, especially across animal hosts. Results We performed a comprehensive codon usage analysis of eight host-specific RVA P genotypes, including human RVA (P[4] and P[8]), porcine RVA (P[13] and P[23]), and zoonotic RVA (P[1], P[6], P[7] and P[19]), based on 233 VP4 complete coding sequences. Nucleotide composition, relative synonymous codon usage (RSCU), and effective number of codons (ENC) were calculated. Principal component analysis (PCA) based on RSCU values was used to explore the codon usage patterns of different RVA P genotypes. In addition, mutation pressure and natural selection were identified by using ENC-plot, parity rule 2 plot, and neutrality plot analyses. All VP4 sequences preferred using A/U nucleotides (A: 0.354-0.377, U: 0.267-0.314) than G/C nucleotides across genotypes. Similarly, majority of commonly used synonymous codons were likely to end with A/U nucleotides (A: 9/18-12/18, U: 6/18-9/18). In PCA, human, porcine, and zoonotic genotypes clustered separately in terms of RSCU values, indicating the host-specific codon usage patterns; however, porcine and zoonotic genotypes were partly overlapped. Human genotypes, P[4] and P[8], had stronger codon usage bias, as indicated by more over-represented codons and lower ENC, compared to porcine and zoonotic genotypes. Moreover, natural selection was determined to be a predominant driver in shaping the codon usage bias across the eight P genotypes. In addition, mutation pressure contributed to the codon usage bias of human genotypes. Conclusions Our study identified a strong codon usage bias of human RVA P genotypes attributable to both natural selection and mutation pressure, whereas similar codon usage bias between porcine and zoonotic genotypes predominantly attributable to natural selection. It further suggests possible cross-species transmission. Therefore, it warrants further surveillance of RVA P genotypes for early identification of zoonotic infection. Supplementary Information The online version contains supplementary material available at 10.1186/s12864-022-08730-2.
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Affiliation(s)
- Han Wu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China
| | - Bingzhe Li
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China
| | - Ziping Miao
- Institute of Communicable Diseases Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310052, Zhejiang, China
| | - Linjie Hu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China
| | - Lu Zhou
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China
| | - Yihan Lu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China.
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25
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Lee B, Colgate ER, Carmolli M, Dickson DM, Gullickson S, Diehl SA, Ara R, Alam M, Kibria G, Abdul Kader M, Afreen S, Ferdous T, Haque R, Kirkpatrick BD. Plasma VP8∗-Binding Antibodies in Rotavirus Infection and Oral Vaccination in Young Bangladeshi Children. J Pediatric Infect Dis Soc 2022; 11:127-133. [PMID: 34904667 PMCID: PMC9055852 DOI: 10.1093/jpids/piab120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/23/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Despite the availability and success of live-attenuated oral vaccines, rotavirus (RV) remains the leading cause of pediatric gastroenteritis worldwide. Next-generation vaccines targeting RV VP8∗ are under evaluation, but the role of VP8∗-specific antibodies in human immunity to RV and their potential as immune correlates of protection remains underexplored. METHODS We measured plasma RV VP8∗-binding antibodies in 2 cohorts of young children in Dhaka, Bangladesh. Plasma from a cohort study of 137 unvaccinated children aged 6-24 months old hospitalized with acute gastroenteritis was assessed for VP8∗ antibody seropositivity. VP8∗ antibodies were compared with the current standard for RV immunity, total RV-specific IgA (RV-IgA). Additionally, VP8∗ antibody responses were measured as part of an immunogenicity trial of a monovalent, oral, live-attenuated RV vaccine (Rotarix). RESULTS Fewer children with acute RV gastroenteritis were seropositive for VP8∗-binding IgA or IgG antibodies at hospital admission compared with RV-IgA, suggesting that the absence of VP8∗-binding antibodies more accurately predicts susceptibility to RV gastroenteritis than RV-IgA in unvaccinated children. However, when present, these antibodies appeared insufficient to protect fully from disease and no threshold antibody level for protection was apparent. In vaccinated children, these antibodies were very poorly induced by Rotarix vaccine, suggesting that VP8∗-specific antibodies alone are not necessary for clinical protection following oral vaccination. CONCLUSIONS This work suggests that VP8∗-binding antibodies may not be sufficient or necessary for protection from RV gastroenteritis following prior RV infection or oral vaccination; the role of VP8∗ antibodies induced by parenteral vaccination with non-replicating vaccines remains to be determined.
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Affiliation(s)
- Benjamin Lee
- Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - E Ross Colgate
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Marya Carmolli
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Dorothy M Dickson
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Soyeon Gullickson
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Sean A Diehl
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Rifat Ara
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Masud Alam
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Golam Kibria
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Md Abdul Kader
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Sajia Afreen
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Tahsin Ferdous
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Rashidul Haque
- Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Beth D Kirkpatrick
- Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.,Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
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26
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Cao H, Wu J, Luan N, Wang Y, Lin K, Liu C. Evaluation of a bivalent recombinant vaccine candidate targeting norovirus and rotavirus: Antibodies to rotavirus NSP4 exert antidiarrheal effects without virus neutralization. J Med Virol 2022; 94:3847-3856. [PMID: 35474320 DOI: 10.1002/jmv.27809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 04/19/2022] [Accepted: 04/23/2022] [Indexed: 11/10/2022]
Abstract
We previously found that when tandemly expressed with SR69A -VP8*, nonstructural protein 4 (NSP4) of the rotavirus Wa strain exerts a minor effect on elevating the antibody responses targeting the rotavirus antigen VP8* of the 60-valent nanoparticle SR69A -VP8* but could fully protect mice from diarrhea induced by the rotavirus strain Wa. In this study, we chose comparably less immunogenic norovirus 24-valent P particles with homogenous (i.e., VP8* from rotavirus) and heterogeneous (i.e., protruding domain of norovirus) antigens and in more challenging rotavirus SA11 strain-induced diarrhea mouse models to evaluate its main role in recombinant gastroenteritis virus-specific vaccines. The results showed that although as an adjuvant NSP4 exerted limited effects on the elevation of norovirus-specific or VP8*-specific neutralizing antibody production, as an antigen it could confer potent protection, particularly when synergized with VP8*, in rotavirus SA11 strain-induced diarrhea mouse models, possibly blocking the invasion of the intestinal wall by enterotoxin. NSP4 may be unnecessary for other recombinant vaccines as adjuvants, and its display mode should be evaluated specifically to avoid blocking coexpressed antigens in the norovirus P particles. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Han Cao
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
| | - Jinyuan Wu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
| | - Ning Luan
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
| | - Yunfei Wang
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
| | - Kangyang Lin
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
| | - Cunbao Liu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan, China
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27
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Omatola CA, Olaniran AO. Rotaviruses: From Pathogenesis to Disease Control-A Critical Review. Viruses 2022; 14:875. [PMID: 35632617 PMCID: PMC9143449 DOI: 10.3390/v14050875] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 12/16/2022] Open
Abstract
Since their first recognition in human cases about four decades ago, rotaviruses have remained the leading cause of acute severe dehydrating diarrhea among infants and young children worldwide. The WHO prequalification of oral rotavirus vaccines (ORV) a decade ago and its introduction in many countries have yielded a significant decline in the global burden of the disease, although not without challenges to achieving global effectiveness. Poised by the unending malady of rotavirus diarrhea and the attributable death cases in developing countries, we provide detailed insights into rotavirus biology, exposure pathways, cellular receptors and pathogenesis, host immune response, epidemiology, and vaccination. Additionally, recent developments on the various host, viral and environmental associated factors impacting ORV performance in low-and middle-income countries (LMIC) are reviewed and their significance assessed. In addition, we review the advances in nonvaccine strategies (probiotics, candidate anti-rotaviral drugs, breastfeeding) to disease prevention and management.
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Affiliation(s)
| | - Ademola O. Olaniran
- Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science, Westville Campus, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa;
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28
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Maeda K, Zachos NC, Orzalli MH, Schmieder SS, Chang D, Bugda Gwilt K, Doucet M, Baetz NW, Lee S, Crawford SE, Estes MK, Kagan JC, Turner JR, Lencer WI. Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces. Cell Host Microbe 2022; 30:216-231.e5. [PMID: 35143768 PMCID: PMC8852832 DOI: 10.1016/j.chom.2021.12.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 10/28/2021] [Accepted: 12/17/2021] [Indexed: 11/22/2022]
Abstract
Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or virus-binding initiates degradation of PARD6B. The loss of PARD6B causes the depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface, thus enabling a form of cell-autonomous host defense.
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Affiliation(s)
- Keiko Maeda
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Nicholas C Zachos
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Megan H Orzalli
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Stefanie S Schmieder
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Denis Chang
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Katlynn Bugda Gwilt
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Michele Doucet
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Nicholas W Baetz
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Sun Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Sue E Crawford
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, MS: BCM-385, Houston, TX 77030, USA
| | - Mary K Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, MS: BCM-385, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
| | - Jonathan C Kagan
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA
| | - Jerrold R Turner
- Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA
| | - Wayne I Lencer
- Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA.
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29
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Amimo JO, Raev SA, Chepngeno J, Mainga AO, Guo Y, Saif L, Vlasova AN. Rotavirus Interactions With Host Intestinal Epithelial Cells. Front Immunol 2021; 12:793841. [PMID: 35003114 PMCID: PMC8727603 DOI: 10.3389/fimmu.2021.793841] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/06/2021] [Indexed: 12/13/2022] Open
Abstract
Rotavirus (RV) is the foremost enteric pathogen associated with severe diarrheal illness in young children (<5years) and animals worldwide. RV primarily infects mature enterocytes in the intestinal epithelium causing villus atrophy, enhanced epithelial cell turnover and apoptosis. Intestinal epithelial cells (IECs) being the first physical barrier against RV infection employs a range of innate immune strategies to counteract RVs invasion, including mucus production, toll-like receptor signaling and cytokine/chemokine production. Conversely, RVs have evolved numerous mechanisms to escape/subvert host immunity, seizing translation machinery of the host for effective replication and transmission. RV cell entry process involve penetration through the outer mucus layer, interaction with cell surface molecules and intestinal microbiota before reaching the IECs. For successful cell attachment and entry, RVs use sialic acid, histo-blood group antigens, heat shock cognate protein 70 and cell-surface integrins as attachment factors and/or (co)-receptors. In this review, a comprehensive summary of the existing knowledge of mechanisms underlying RV-IECs interactions, including the role of gut microbiota, during RV infection is presented. Understanding these mechanisms is imperative for developing efficacious strategies to control RV infections, including development of antiviral therapies and vaccines that target specific immune system antagonists within IECs.
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Affiliation(s)
- Joshua Oluoch Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - Sergei Alekseevich Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Juliet Chepngeno
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Alfred Omwando Mainga
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
- Department of Public Health, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - Yusheng Guo
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Linda Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Anastasia N. Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
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30
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Peña-Gil N, Santiso-Bellón C, Gozalbo-Rovira R, Buesa J, Monedero V, Rodríguez-Díaz J. The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update. Int J Mol Sci 2021; 22:13473. [PMID: 34948268 PMCID: PMC8704558 DOI: 10.3390/ijms222413473] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/13/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.
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Affiliation(s)
- Nazaret Peña-Gil
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Cristina Santiso-Bellón
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Roberto Gozalbo-Rovira
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Javier Buesa
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Vicente Monedero
- Department of Biotechnology, Institute of Agrochemistry and Food Technology (IATA-CSIC), 46980 Paterna, Spain;
| | - Jesús Rodríguez-Díaz
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
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31
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Patra U, Mukhopadhyay U, Mukherjee A, Dutta S, Chawla-Sarkar M. Treading a HOSTile path: Mapping the dynamic landscape of host cell-rotavirus interactions to explore novel host-directed curative dimensions. Virulence 2021; 12:1022-1062. [PMID: 33818275 PMCID: PMC8023246 DOI: 10.1080/21505594.2021.1903198] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/20/2021] [Accepted: 03/10/2021] [Indexed: 12/27/2022] Open
Abstract
Viruses are intracellular pathogens and are dependent on host cellular resources to carry out their cycles of perpetuation. Obtaining an integrative view of host-virus interaction is of utmost importance to understand the complex and dynamic interplay between viral components and host machineries. Besides its obvious scholarly significance, a comprehensive host-virus interaction profile also provides a platform where from host determinants of pro-viral and antiviral importance can be identified and further be subjected to therapeutic intervention. Therefore, adjunct to conventional methods of prophylactic vaccination and virus-directed antivirals, this host-targeted antiviral approach holds promising therapeutic potential. In this review, we present a comprehensive landscape of host cellular reprogramming in response to infection with rotavirus (RV) which causes profuse watery diarrhea in neonates and infants. In addition, an emphasis is given on how host determinants are either usurped or subverted by RV in course of infection and how therapeutic manipulation of specific host factors can effectively modulate the RV life cycle.
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Affiliation(s)
- Upayan Patra
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India
| | - Urbi Mukhopadhyay
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India
| | - Arpita Mukherjee
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India
| | - Shanta Dutta
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India
| | - Mamta Chawla-Sarkar
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India
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32
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Caddy S, Papa G, Borodavka A, Desselberger U. Rotavirus research: 2014-2020. Virus Res 2021; 304:198499. [PMID: 34224769 DOI: 10.1016/j.virusres.2021.198499] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 02/09/2023]
Abstract
Rotaviruses are major causes of acute gastroenteritis in infants and young children worldwide and also cause disease in the young of many other mammalian and of avian species. During the recent 5-6 years rotavirus research has benefitted in a major way from the establishment of plasmid only-based reverse genetics systems, the creation of human and other mammalian intestinal enteroids, and from the wide application of structural biology (cryo-electron microscopy, cryo-EM tomography) and complementary biophysical approaches. All of these have permitted to gain new insights into structure-function relationships of rotaviruses and their interactions with the host. This review follows different stages of the viral replication cycle and summarizes highlights of structure-function studies of rotavirus-encoded proteins (both structural and non-structural), molecular mechanisms of viral replication including involvement of cellular proteins and lipids, the spectrum of viral genomic and antigenic diversity, progress in understanding of innate and acquired immune responses, and further developments of prevention of rotavirus-associated disease.
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Affiliation(s)
- Sarah Caddy
- Cambridge Institute for Therapeutic Immunology and Infectious Disease Jeffery Cheah Biomedical Centre, Cambridge, CB2 0AW, UK.
| | - Guido Papa
- MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus Francis Crick Avenue, Cambridge, CB2 0QH, UK.
| | - Alexander Borodavka
- Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK.
| | - Ulrich Desselberger
- Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
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33
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Tenge VR, Hu L, Prasad BVV, Larson G, Atmar RL, Estes MK, Ramani S. Glycan Recognition in Human Norovirus Infections. Viruses 2021; 13:2066. [PMID: 34696500 PMCID: PMC8537403 DOI: 10.3390/v13102066] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 12/11/2022] Open
Abstract
Recognition of cell-surface glycans is an important step in the attachment of several viruses to susceptible host cells. The molecular basis of glycan interactions and their functional consequences are well studied for human norovirus (HuNoV), an important gastrointestinal pathogen. Histo-blood group antigens (HBGAs), a family of fucosylated carbohydrate structures that are present on the cell surface, are utilized by HuNoVs to initially bind to cells. In this review, we describe the discovery of HBGAs as genetic susceptibility factors for HuNoV infection and review biochemical and structural studies investigating HuNoV binding to different HBGA glycans. Recently, human intestinal enteroids (HIEs) were developed as a laboratory cultivation system for HuNoV. We review how the use of this novel culture system has confirmed that fucosylated HBGAs are necessary and sufficient for infection by several HuNoV strains, describe mechanisms of antibody-mediated neutralization of infection that involve blocking of HuNoV binding to HBGAs, and discuss the potential for using the HIE model to answer unresolved questions on viral interactions with HBGAs and other glycans.
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Affiliation(s)
- Victoria R. Tenge
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
| | - Liya Hu
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA;
| | - B. V. Venkataram Prasad
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Göran Larson
- Department of Laboratory Medicine, University of Gothenburg, SE 413 45 Gothenburg, Sweden;
| | - Robert L. Atmar
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Mary K. Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sasirekha Ramani
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
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34
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Kanai Y, Kobayashi T. FAST Proteins: Development and Use of Reverse Genetics Systems for Reoviridae Viruses. Annu Rev Virol 2021; 8:515-536. [PMID: 34586868 DOI: 10.1146/annurev-virology-091919-070225] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Reverse genetics systems for viruses, the technology used to generate gene-engineered recombinant viruses from artificial genes, enable the study of the roles of the individual nucleotides and amino acids of viral genes and proteins in infectivity, replication, and pathogenicity. The successful development of a reverse genetics system for poliovirus in 1981 accelerated the establishment of protocols for other RNA viruses important for human health. Despite multiple efforts, rotavirus (RV), which causes severe gastroenteritis in infants, was refractory to reverse genetics analysis, and the first complete reverse genetics system for RV was established in 2017. This novel technique involves use of the fusogenic protein FAST (fusion-associated small transmembrane) derived from the bat-borne Nelson Bay orthoreovirus, which induces massive syncytium formation. Co-transfection of a FAST-expressing plasmid with complementary DNAs encoding RV genes enables rescue of recombinant RV. This review focuses on methodological insights into the reverse genetics system for RV and discusses applications and potential improvements to this system.
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Affiliation(s)
- Yuta Kanai
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; ,
| | - Takeshi Kobayashi
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; ,
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35
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Dang L, Su Y, Qi J, Wu Z, Li D, Wang M, Zhang Q, Wang H, Bai R, Duan Z, Sun X. Structural and functional characterization of bovine G1P[5] rotavirus VP8* protein. Virology 2021; 563:116-125. [PMID: 34509703 DOI: 10.1016/j.virol.2021.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/07/2021] [Accepted: 08/17/2021] [Indexed: 11/26/2022]
Abstract
The widely used rotavirus (RV) vaccine, Rotateq, contained reassortment strains of human and bovine G1/2/3/4P[5] RVs. The functional and structural features of bovine G1P[5] VP8* were investigated. Bovine G1P[5] VP8* was identified to interact with sialic acids and sialic acid-containing glycans. In addition, P[5] VP8* recognized α-Gal histo-blood group antigens (HBGAs). Bovine G1P[5] VP8* did not hemagglutinate the tested red blood cells. The crystal structure of P[5] VP8* was determined at 1.7 Å. Structural superimposition revealed that P[5] VP8* was most close to human P[8] VP8*, while much further to VP8*s of porcine P[7] and rhesus P[3]. Sequence alignment showed that amino acids of the putative glycan binding site in P[5] VP8* were different to those in P[3]/P[7] VP8*s, indicating that P[5] VP8* may interact with glycans using different mechanism. This study provided more understanding of P[5] RV infection and the interactions of RV VP8* and glycans.
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Affiliation(s)
- Lei Dang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China; Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, 010059, China
| | - Yunxi Su
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Jianxun Qi
- Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Zheng Wu
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Dandi Li
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Mengxuan Wang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Qing Zhang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Hong Wang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Ruixia Bai
- Inner Mongolia Medical University, Hohhot, 010059, China
| | - Zhaojun Duan
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.
| | - Xiaoman Sun
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.
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36
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Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens. Proc Natl Acad Sci U S A 2021; 118:2107963118. [PMID: 34475219 DOI: 10.1073/pnas.2107963118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/02/2021] [Indexed: 12/27/2022] Open
Abstract
Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor-binding domains together with Lewis epitope-containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ββ and βα HBGA receptor-binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.
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37
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Sun X, Li D, Duan Z. Structural Basis of Glycan Recognition of Rotavirus. Front Mol Biosci 2021; 8:658029. [PMID: 34307449 PMCID: PMC8296142 DOI: 10.3389/fmolb.2021.658029] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/21/2021] [Indexed: 11/13/2022] Open
Abstract
Rotavirus (RV) is an important pathogen causing acute gastroenteritis in young humans and animals. Attachment to the host receptor is a crucial step for the virus infection. The recent advances in illustrating the interactions between RV and glycans promoted our understanding of the host range and epidemiology of RVs. VP8*, the distal region of the RV outer capsid spike protein VP4, played a critical role in the glycan recognition. Group A RVs were classified into different P genotypes based on the VP4 sequences and recognized glycans in a P genotype-dependent manner. Glycans including sialic acid, gangliosides, histo-blood group antigens (HBGAs), and mucin cores have been reported to interact with RV VP8*s. The glycan binding specificities of VP8*s of different RV genotypes have been studied. Here, we mainly discussed the structural basis for the interactions between RV VP8*s and glycans, which provided molecular insights into the receptor recognition and host tropism, offering new clues to the design of RV vaccine and anti-viral agents.
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Affiliation(s)
- Xiaoman Sun
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
| | - Dandi Li
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
| | - Zhaojun Duan
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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38
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Martynov I, Göpel W, Rausch TK, Härtel C, Franke A, Franz AR, Viemann D, Thome UH, Lacher M, Ackermann BW. Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight. Sci Rep 2021; 11:13777. [PMID: 34215818 PMCID: PMC8253726 DOI: 10.1038/s41598-021-93195-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 06/14/2021] [Indexed: 12/13/2022] Open
Abstract
Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07–2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06–3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10–2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.
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Affiliation(s)
- I Martynov
- Department of Pediatric Surgery, University of Leipzig, Liebigstraße 20 a, 04103, Leipzig, Germany.
| | - W Göpel
- Department of Pediatrics, University of Lübeck, Lübeck, Germany
| | - T K Rausch
- Department of Pediatrics, University of Lübeck, Lübeck, Germany.,Institute for Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany
| | - C Härtel
- Department of Pediatrics, University of Lübeck, Lübeck, Germany
| | - A Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Kiel, Germany
| | - A R Franz
- Department of Neonatology, University Children's Hospital Tübingen, Tübingen, Germany.,Center for Pediatric Clinical Studies (CPCS), University Children's Hospital Tübingen, Tübingen, Germany
| | - D Viemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - U H Thome
- Division of Neonatology, Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
| | - M Lacher
- Department of Pediatric Surgery, University of Leipzig, Liebigstraße 20 a, 04103, Leipzig, Germany
| | - B W Ackermann
- Division of Neonatology, Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
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39
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Sharma S, Nordgren J. Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take-An Overview. Viruses 2021; 13:1144. [PMID: 34198720 PMCID: PMC8232156 DOI: 10.3390/v13061144] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023] Open
Abstract
Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.
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Affiliation(s)
| | - Johan Nordgren
- Division of Molecular Medicine and Virology, Department of Clinical and Biomedical Sciences, Linköping University, 58183 Linköping, Sweden;
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Kondakova OA, Ivanov PA, Baranov OA, Ryabchevskaya EM, Arkhipenko MV, Skurat EV, Evtushenko EA, Nikitin NA, Karpova OV. Novel antigen panel for modern broad-spectrum recombinant rotavirus A vaccine. Clin Exp Vaccine Res 2021; 10:123-131. [PMID: 34222124 PMCID: PMC8217573 DOI: 10.7774/cevr.2021.10.2.123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/14/2021] [Accepted: 02/15/2021] [Indexed: 11/17/2022] Open
Abstract
Purpose Recombinant rotavirus A vaccines are being developed as an alternative to existing live oral attenuated vaccines. One of the main problems in the production of such vaccines is the genetic diversity of the strains that are in circulation. The goal of this study was to create an antigen panel for modern broad-spectrum recombinant rotavirus A vaccine. Materials and Methods The antigens of rotavirus were cloned and expressed in Escherichia coli. Antigenic specificity was investigated by Western blot analysis, which was performed using commercial polyclonal antisera to several RVA strains. Phylogenetic analysis was based on the amino acid sequences of the VP8* protein fragment of human RVA isolates representing genotypes P[4], P[6], and P[8]. Results A universal panel of antigens was established, including consensus and conserved sequences of structural proteins VP8*, VP5*, and VP7, which are the main targets of neutralizing antibodies. For the first time, a consensus approach was used in the design of extended antigens based on VP8* (genotypes P[4], P[6], and P[8]) and VP5* (genotype P[8]) proteins' fragments. In addition, a gene coding the protein (ep-875) containing several copies of conserved short neutralizing epitopes of VP8*, VP7, and VP5* was created. Western blot analysis demonstrated that three synthetic VP8*-based antigens were not recognized by commercial antiserum against rotavirus strains isolated more than 35 years ago, but the specific activity of the VP5* and ep-875 antigens was confirmed. The problems of serological mismatch of vaccine strains and antigens with currently circulating strains are discussed. Conclusion Five antigens representing sequences of structural proteins belonging to different genotypes can be used in various combinations (from mono- to pentavalent mixtures) for the development of an effective broad-spectrum rotavirus vaccine.
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Affiliation(s)
- Olga A Kondakova
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Peter A Ivanov
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Oleg A Baranov
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Ekaterina M Ryabchevskaya
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Marina V Arkhipenko
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Eugene V Skurat
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Ekaterina A Evtushenko
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Nikolai A Nikitin
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
| | - Olga V Karpova
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
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Cárcamo-Calvo R, Muñoz C, Buesa J, Rodríguez-Díaz J, Gozalbo-Rovira R. The Rotavirus Vaccine Landscape, an Update. Pathogens 2021; 10:520. [PMID: 33925924 PMCID: PMC8145439 DOI: 10.3390/pathogens10050520] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/21/2021] [Accepted: 04/23/2021] [Indexed: 11/17/2022] Open
Abstract
Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.
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Affiliation(s)
- Roberto Cárcamo-Calvo
- Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010 Valencia, Spain; (R.C.-C.); (C.M.); (J.B.)
| | - Carlos Muñoz
- Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010 Valencia, Spain; (R.C.-C.); (C.M.); (J.B.)
| | - Javier Buesa
- Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010 Valencia, Spain; (R.C.-C.); (C.M.); (J.B.)
- Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
| | - Jesús Rodríguez-Díaz
- Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010 Valencia, Spain; (R.C.-C.); (C.M.); (J.B.)
- Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
| | - Roberto Gozalbo-Rovira
- Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010 Valencia, Spain; (R.C.-C.); (C.M.); (J.B.)
- Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
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Zhao D, Liu Y, Huang P, Xia M, Li W, Tan M, Zhang X, Jiang X. Histo-blood group antigens as divergent factors of groups A and C rotaviruses circulating in humans and different animal species. Emerg Microbes Infect 2021; 9:1609-1617. [PMID: 32543972 PMCID: PMC7473324 DOI: 10.1080/22221751.2020.1782270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.
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Affiliation(s)
- Dandan Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangdong, People's Republic of China
| | - Yang Liu
- Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ming Xia
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Weiwei Li
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - XuFu Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangdong, People's Republic of China
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Rossouw E, Brauer M, Meyer P, du Plessis NM, Avenant T, Mans J. Virus Etiology, Diversity and Clinical Characteristics in South African Children Hospitalised with Gastroenteritis. Viruses 2021; 13:v13020215. [PMID: 33573340 PMCID: PMC7911269 DOI: 10.3390/v13020215] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/26/2021] [Accepted: 01/27/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Viral gastroenteritis remains a major cause of hospitalisation in young children. This study aimed to determine the distribution and diversity of enteric viruses in children ≤5 years, hospitalised with gastroenteritis at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa, between July 2016 and December 2017. METHODS Stool specimens (n = 205) were screened for norovirus GI and GII, rotavirus, sapovirus, astrovirus and adenovirus by multiplex RT-PCR. HIV exposure and FUT2 secretor status were evaluated. Secretor status was determined by FUT2 genotyping. RESULTS At least one gastroenteritis virus was detected in 47% (96/205) of children. Rotavirus predominated (46/205), followed by norovirus (32/205), adenovirus (15/205), sapovirus (9/205) and astrovirus (3/205). Norovirus genotypes GI.3, GII.2, GII.3, GII.4, GII.7, GII.12, GII.21, and rotavirus strains G1P[8], G2P[4], G2P[6], G3P[4], G3P[8], G8P[4], G8P[6], G9P[6], G9P[8] and sapovirus genotypes GI.1, GI.2, GII.1, GII.4, GII.8 were detected; norovirus GII.4[P31] and rotavirus G3P[4] predominated. Asymptomatic norovirus infection (GI.3, GI.7, GII.4, GII.6, GII.13) was detected in 22% of 46 six-week follow up stools. HIV exposure (30%) was not associated with more frequent or severe viral gastroenteritis hospitalisations compared to unexposed children. Rotavirus preferentially infected secretor children (p = 0.143) and norovirus infected 78% secretors and 22% non-secretors. CONCLUSION Rotavirus was still the leading cause of gastroenteritis hospitalisations, but norovirus caused more severe symptoms.
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Affiliation(s)
- Esmari Rossouw
- Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa;
| | - Marieke Brauer
- Immunology Laboratory, Ampath, Pretoria 0001, South Africa;
| | - Pieter Meyer
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa or
- National Health Laboratory Service, Tshwane Academic Division, Pretoria 0001, South Africa
| | - Nicolette M. du Plessis
- Department of Paediatrics, Kalafong Provincial Tertiary Hospital, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (N.M.d.P.); (T.A.)
| | - Theunis Avenant
- Department of Paediatrics, Kalafong Provincial Tertiary Hospital, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (N.M.d.P.); (T.A.)
| | - Janet Mans
- Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa;
- Correspondence: ; Tel.: +27-12-319-2660
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Infection of porcine small intestinal enteroids with human and pig rotavirus A strains reveals contrasting roles for histo-blood group antigens and terminal sialic acids. PLoS Pathog 2021; 17:e1009237. [PMID: 33513201 PMCID: PMC7846020 DOI: 10.1371/journal.ppat.1009237] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/15/2020] [Indexed: 01/19/2023] Open
Abstract
Rotaviruses (RVs) are a leading cause of acute viral gastroenteritis in young children and livestock worldwide. Growing evidence suggests that host cellular glycans, such as histo-blood group antigens (HBGAs) and sialic acids (SA), are recognized by the RV surface protein VP4. However, a mechanistic understanding of these interactions and their effects on RV infection and pathogenesis is lacking. Here, we established a porcine crypt-derived 3Dintestinalenteroids (PIEs) culture system which contains all intestinal epithelial cells identified in vivo and represents a unique physiologically functional model to study RV-glycan interactions in vitro. PIEs expressing different HBGAs (A+, H+, and A+/H+) were established and isolation, propagation, differentiation and RV infection conditions were optimized. Differentiated PIEs were infected with human RV (HRV) G1P[8] Wa, porcine RV (PRV) G9P[13], PRV Gottfried G4P[6] or PRV OSU G5P[7] virulent and attenuated strains and virus replication was measured by qRT-PCR. Our results indicated that virulent HRV G1P[8] Wa replicated to the highest titers in A+ PIEs, while a distinct trend was observed for PRV G9P[13] or G5P[7] with highest titers in H+ PIEs. Attenuated Wa and Gottfried strains replicated poorly in PIEs while the replication of attenuated G9P[13] and OSU strains in PIEs was relatively efficient. However, the replication of all 4 attenuate strains was less affected by the PIE HBGA phenotypes. HBGA synthesis inhibitor 2-F-Peracetyl-Fucose (2F) treatment demonstrated that HBGAs are essential for G1P[8] Wa replication; however, they may only serve as a cofactor for PRVs G9P[13] and OSU G5P[7]. Interestingly, contrasting outcomes were observed following sialidase treatment which significantly enhanced G9P[13] replication, but inhibited the growth of G5P[7]. These observations suggest that some additional receptors recognized by G9P[13] become unmasked after removal of terminal SA. Overall, our results confirm that differential HBGAs-RV and SA-RV interactions determine replication efficacy of virulent group A RVs in PIEs. Consequently, targeting individual glycans for development of therapeutics may not yield uniform results for various RV strains. Cell surface glycans, including histo-blood group antigens (HBGA) and sialic acids (SAs), have been shown to serve as receptors/attachment factors for many pathogens including RVs. However, how those glycans affect RV replication remains largely unknown due the lack of reliable in vitro models. To solve this problem, we established a 3D porcine intestinal enteroid (PIE) model that recapitulates the complex intestinal morphology better than conventional cell lines. By utilizing PIEs expressing different types of HBGAs, we found that several RV strains including Wa G1P[8], OSU G5P[7] and G9P[13] show preference for certain HBGA types. Interestingly, only Wa replication was reduced when HBGAs synthesis was inhibited, while that of OSU and G9P[13] was only marginally affected, which indicates that they may utilize alternative attachment factors for infection. Sialidase treatment strongly inhibited the growth of OSU, while G9P[13] replication was significantly enhanced. These findings suggest that SAs play contrasting roles in the infection of PRV OSU and G9P[13] strains. Overall, our studies demonstrate that PIEs can serve as a model to study pathogen-glycan interactions and suggest that genetically distinct RVs have evolved diverse mechanisms of cell attachment and/or entry.
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Farahmand M, Jalilvand S, Arashkia A, Shahmahmoodi S, Afchangi A, Mollaei-Kandelous Y, Shoja Z. Association between circulating rotavirus genotypes and histo-blood group antigens in the children hospitalized with acute gastroenteritis in Iran. J Med Virol 2021; 93:4817-4823. [PMID: 33463743 DOI: 10.1002/jmv.26808] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/09/2020] [Accepted: 01/17/2021] [Indexed: 12/16/2022]
Abstract
Rotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo-blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to P[II]. The most common genotype was P[8] (n = 102; 94.4%), while the remaining belonged to P[4] (n = 3; 2.8%) and P[6] (n = 3; 2.8%) genotypes. The P[8] genotype was found to be associated with secretor and Lewis positive status (p < .05).
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Affiliation(s)
- Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Jalilvand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Arashkia
- Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Shohreh Shahmahmoodi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Atefeh Afchangi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Zabihollah Shoja
- Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
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Liu C, Huang P, Zhao D, Xia M, Zhong W, Jiang X, Tan M. Effects of rotavirus NSP4 protein on the immune response and protection of the S R69A-VP8* nanoparticle rotavirus vaccine. Vaccine 2021; 39:263-271. [PMID: 33309483 PMCID: PMC7822095 DOI: 10.1016/j.vaccine.2020.12.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 11/05/2020] [Accepted: 12/01/2020] [Indexed: 12/14/2022]
Abstract
Rotavirus causes severe diarrhea and dehydration in young children. Even with the implementation of the current live vaccines, rotavirus infections still cause significant mortality and morbidity, indicating a need for new rotavirus vaccines with improved efficacy. To this end, we have developed an SR69A-VP8*/S60-VP8* nanoparticle rotavirus vaccine candidate that will be delivered parenterally with Alum adjuvant. In this study, as parts of our further development of this nanoparticle vaccine, we evaluated 1) roles of rotavirus nonstructural protein 4 (NSP4) that is the rotavirus enterotoxin, a possible vaccine target, and an immune stimulator, and 2) effects of CpG adjuvant that is a toll-like receptor 9 (TLR9) ligand and agonist on the immune response and protection of our SR69A-VP8*/S60-VP8* nanoparticle vaccine. The resulted vaccine candidates were examined for their IgG responses in mice. In addition, the resulted mouse sera were assessed for i) blocking titers against interactions of rotavirus VP8* proteins with their glycan ligands, ii) neutralization titers against rotavirus replication in cell culture, and iii) passive protection against rotavirus challenge with diarrhea in suckling mice. Our data showed that the Alum adjuvant appeared to work better with the SR69A-VP8*/S60-VP8* nanoparticles than the CpG adjuvant, while an addition of the NSP4 antigen to the SR69A-VP8*/S60-VP8* vaccine may not help to further increase the immune response and protection of the resulted vaccine.
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Affiliation(s)
- Cunbao Liu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan Province, China
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Dandan Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Ming Xia
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Weiming Zhong
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Xia M, Huang P, Jiang X, Tan M. A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses. Viruses 2021; 13:72. [PMID: 33419150 PMCID: PMC7825513 DOI: 10.3390/v13010072] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 01/02/2021] [Accepted: 01/04/2021] [Indexed: 12/27/2022] Open
Abstract
Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.
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Affiliation(s)
- Ming Xia
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; (M.X.); (P.H.)
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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Human group A rotavirus P[25] VP8* specifically binds to A-type histo-blood group antigen. Virology 2021; 555:56-63. [PMID: 33453651 DOI: 10.1016/j.virol.2020.12.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 11/12/2020] [Accepted: 12/24/2020] [Indexed: 11/21/2022]
Abstract
Rotavirus (RV) is a common cause of acute gastroenteritis in young children. While P[8] and P[4] are the most prevalent RV genotypes in humans, other genotypes are also reported in human infections occasionally, including human P[25]. The glycan binding and structural characteristics of human P[25] were explored in our study. Human P[25] VP8* recognized type A histo-blood group antigen (HBGA) in the glycan microarray/oligosaccharide binding assay and could specifically hemagglutinate type A blood cells. Moreover, the P[25] VP8* structure was determined at 2.6 Å, revealing a similar conformation and a conserved putative glycan binding site as that of P[14] VP8*. This study provided further knowledge of the glycan binding and structural features of P[25] RV VP8*, promoting our understanding of the infection, prevalence, and host range of the P[III] RVs.
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50
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Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines. Vaccines (Basel) 2020; 8:vaccines8030341. [PMID: 32604982 PMCID: PMC7565912 DOI: 10.3390/vaccines8030341] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/26/2020] [Accepted: 05/26/2020] [Indexed: 12/15/2022] Open
Abstract
Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix®, RotaTeq®, Rotavac®, and RotaSIIL®) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines.
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