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Kafeero HM, Ndagire D, Ocama P, Kato CD, Wampande E, Walusansa A, Kajumbula H, Kateete D, Ssenku JE, Sendagire H. Mapping hepatitis B virus genotypes on the African continent from 1997 to 2021: a systematic review with meta-analysis. Sci Rep 2023; 13:5723. [PMID: 37029173 PMCID: PMC10082212 DOI: 10.1038/s41598-023-32865-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/04/2023] [Indexed: 04/09/2023] Open
Abstract
Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.
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Affiliation(s)
- Hussein Mukasa Kafeero
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda.
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda.
| | - Dorothy Ndagire
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Charles Drago Kato
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Eddie Wampande
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Abdul Walusansa
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
| | - Henry Kajumbula
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - David Kateete
- Department of Molecular Biology and Immunology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Jamilu E Ssenku
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Hakim Sendagire
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
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2
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Trovão NS, Thijssen M, Vrancken B, Pineda-Peña AC, Mina T, Amini-Bavil-Olyaee S, Lemey P, Baele G, Pourkarim MR. Reconstruction of the Origin and Dispersal of the Worldwide Dominant Hepatitis B Virus Subgenotype D1. Virus Evol 2022; 8:veac028. [PMID: 35712523 PMCID: PMC9194798 DOI: 10.1093/ve/veac028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 02/18/2022] [Accepted: 04/07/2022] [Indexed: 12/01/2022] Open
Abstract
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV-D1 is the dominant subgenotype in the Mediterranean basin, Eastern Europe, and Asia. However, little is currently known about its evolutionary history and spatio-temporal dynamics. We use Bayesian phylodynamic inference to investigate the temporal history of HBV-D1, for which we calibrate the molecular clock using ancient sequences, and reconstruct the viral global spatial dynamics based, for the first time, on full-length publicly available HBV-D1 genomes from a wide range of sampling dates. We pinpoint the origin of HBV subgenotype D1 before the current era (BCE) in Turkey/Anatolia. The spatial reconstructions reveal global viral transmission with a high degree of mixing. By combining modern-day and ancient sequences, we ensure sufficient temporal signal in HBV-D1 data to enable Bayesian phylodynamic inference using a molecular clock for time calibration. Our results shed light on the worldwide HBV-D1 epidemics and suggest that this originally Middle Eastern virus significantly affects more distant countries, such as those in mainland Europe.
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Affiliation(s)
- Nídia Sequeira Trovão
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
| | - Marijn Thijssen
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
| | - Bram Vrancken
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
| | - Andrea-Clemencia Pineda-Peña
- Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT; Universidade Nova de Lisboa, UNL, Lisbon, Portugal Rua da Junqueira No 100, 1349-008, Lisbon, Portugal
- Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC); Faculty of Animal Science, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A), Avenida 50 No. 26-20 Bogotá, Colombia
| | - Thomas Mina
- Mina Clinical Laboratory, Gregori Afxentiou, Iocasti Court Block A, Flat 22 Mesa Yitonia, 4003 Lemesos, Cyprus
| | - Samad Amini-Bavil-Olyaee
- Biosafety Development Group, Cellular Sciences Department, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
| | - Philippe Lemey
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
| | - Guy Baele
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
| | - Mahmoud Reza Pourkarim
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium, Herestraat 49, BE-3000 Leuven, Belgium
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
- Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Hemmat Exp. Way, 14665-1157, Tehran, Iran
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3
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Toyé RM, Cohen D, Pujol FH, Sow-Sall A, Lô G, Hoshino K, Mizokami M, Zoulim F, Lemoine M, Touré-Kane C, Chemin I. Hepatitis B Virus Genotype Study in West Africa Reveals an Expanding Clade of Subgenotype A4. Microorganisms 2021; 9:623. [PMID: 33803011 PMCID: PMC8002614 DOI: 10.3390/microorganisms9030623] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/13/2021] [Accepted: 03/15/2021] [Indexed: 01/04/2023] Open
Abstract
Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences.
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Affiliation(s)
- Rayana Maryse Toyé
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, CRCL, 151 Cours Albert Thomas, 69003 Lyon, France; (D.C.); (F.Z.)
- Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (Iressef), BP 7325, Diamniadio 20000, Senegal; (A.S.-S.); (G.L.); (C.T.-K.)
| | - Damien Cohen
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, CRCL, 151 Cours Albert Thomas, 69003 Lyon, France; (D.C.); (F.Z.)
| | - Flor Helene Pujol
- Laboratorio de Virología Molecular, CMBC, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020A, Venezuela;
| | - Amina Sow-Sall
- Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (Iressef), BP 7325, Diamniadio 20000, Senegal; (A.S.-S.); (G.L.); (C.T.-K.)
| | - Gora Lô
- Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (Iressef), BP 7325, Diamniadio 20000, Senegal; (A.S.-S.); (G.L.); (C.T.-K.)
| | - Kunikazu Hoshino
- Department of Infectious, Respiratory, and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan;
| | - Masashi Mizokami
- Research Institute, Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan;
| | - Fabien Zoulim
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, CRCL, 151 Cours Albert Thomas, 69003 Lyon, France; (D.C.); (F.Z.)
| | - Maud Lemoine
- Division of Digestive Diseases, St Mary’s Hospital, Imperial College London, London SW7 2AZ, UK;
| | - Coumba Touré-Kane
- Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (Iressef), BP 7325, Diamniadio 20000, Senegal; (A.S.-S.); (G.L.); (C.T.-K.)
| | - Isabelle Chemin
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, CRCL, 151 Cours Albert Thomas, 69003 Lyon, France; (D.C.); (F.Z.)
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Feng Y, Ran J, Feng YM, Miao J, Zhao Y, Jia Y, Li Z, Yue W, Xia X. Genetic diversity of hepatitis B virus in Yunnan, China: identification of novel subgenotype C17, an intergenotypic B/I recombinant, and B/C recombinants. J Gen Virol 2021; 101:972-981. [PMID: 30252642 DOI: 10.1099/jgv.0.001147] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Yunnan is considered to be a geographical hotspot for the introduction, mutation and recombination of several viruses in China. However, there are limited data regarding the genotypic profiles of hepatitis B virus (HBV) in this region. In this study, we characterized 206 HBV strains isolated from chronic hepatitis B patients in Yunnan, China. Initial genotyping based on 1.5 kb sequences revealed that genotype C was the most prevalent at 52.4 % (108/206), followed by genotype B at 30.6 % (63/206) and unclassified genotypes at 17.0 % (35/206). To characterize the 35 unclassified strains, 32 complete HBV genomes were amplified and analysed; 17 isolates were classified within a known subgenotype, 8 were classified as B/C recombinants, 1 was classified as a B/I recombinant and 6 constituted a potentially novel C subgenotype that we designated as C17, based on the characteristics of a monophyletic cluster, >4 % genetic distances, no significant evidence of recombination and no epidemiological link among individuals. Thus, multiple subgenotypes - namely B1, B2, B4, C1, C2, C3, C4, C8 and C17 - and two distinct intergenotypic recombinants exist in Yunnan, China, highlighting the complex and diverse distribution pattern of HBV genotypic profiles.
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Affiliation(s)
- Yue Feng
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
| | - Jieyu Ran
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
| | - Yue-Mei Feng
- Research Institute of Nutrition and Food Science, Kunming Medical University, Kunming, Yunnan 650500, PR China
| | - Jing Miao
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
| | - Yue Zhao
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
| | - Yuanyuan Jia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
| | - Zheng Li
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan, PR China
| | - Wei Yue
- Department of Infectious Disease, The First People's Hospital of Yunnan Province, Kunming, Yunnan, PR China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, PR China
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5
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Abe H, Ushijima Y, Bikangui R, Loembe MM, Agnandji ST, de Vries SG, Grobusch MP, Lell B, Yasuda J. Ongoing evolution of hepatitis B virus during viremia in patients with febrile in Central Africa. J Med Virol 2019; 92:251-256. [PMID: 31538666 DOI: 10.1002/jmv.25598] [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: 04/09/2019] [Accepted: 09/16/2019] [Indexed: 11/08/2022]
Abstract
Hepatitis B virus (HBV) infection remains to be a major public health issue worldwide, although there is currently a safe vaccine and effective antiviral treatments. In surveillance of infectious diseases in Gabon, HBV viremia was detected in patients with febrile. Whole-genome sequencing was conducted to characterize the HBV strains currently circulating in Gabon and to investigate HBV genome diversity during viremia. Phylogenetic analysis revealed the existence of former subgenotype A5, which exhibits a particular pattern of distribution from several West and Central African countries to Haiti. Furthermore, sequencing analysis identified two similar HBV strains mixed in one sample, and a very rare 1-base pair insertion in the viral precore region. This insertion caused a frameshift mutation, indicating the production of an aberrant fusion protein of the HBV x and e antigens. Our data showed that the detected HBV strain was possibly in an "evolving" state during viremia, a phase of active replication.
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Affiliation(s)
- Haruka Abe
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan
| | - Yuri Ushijima
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan
| | - Rodrigue Bikangui
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.,Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Marguerite M Loembe
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.,Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.,Université des Sciences de la Santé de Libreville, Libreville, Gabon
| | - Selidji T Agnandji
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.,Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Sophia G de Vries
- Division of Internal Medicine, Department of Infectious Diseases, Center of Tropical Medicine and Travel Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Martin P Grobusch
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.,Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.,Division of Internal Medicine, Department of Infectious Diseases, Center of Tropical Medicine and Travel Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Bertrand Lell
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.,Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.,Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Jiro Yasuda
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.,National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki, Japan.,Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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6
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Pennap GR, Mohammed HI, Oti VB, Adoga MP. Genotype distribution of hepatitis B virus in a subset of infected young people in Central Nigeria. SCIENTIFIC AFRICAN 2019. [DOI: 10.1016/j.sciaf.2019.e00122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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7
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Atsama Amougou M, Marchio A, Bivigou-Mboumba B, Noah Noah D, Banai R, Atangana PJA, Fewou Moundipa P, Pineau P, Njouom R. Enrichment in selected genotypes, basal core and precore mutations of hepatitis B virus in patients with hepatocellular carcinoma in Cameroon. J Viral Hepat 2019; 26:1086-1093. [PMID: 31106515 DOI: 10.1111/jvh.13131] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/18/2019] [Accepted: 05/03/2019] [Indexed: 12/21/2022]
Abstract
Worldwide, the development of hepatocellular carcinoma (HCC) is known to be influenced by several hepatitis B viral factors. However, the effect of hepatitis B virus (HBV) genotypes and a landscape of nucleotide changes affecting the precore (PC) and basal core promoter (BCP) during infection leading to HCC remain largely unknown in the Central Africa region. Thus, we performed a case-control study on patients with HBV-related HCC and matched controls without HCC but with chronic HBV infection. Genotypes and mutation spectrums were evaluated using a hemi-nested amplification and sequencing analysis focused on the BCP and PC regions. We identified the co-circulation of HBV quasi-subgenotype A3 (QS-A3) and genotype E in both groups. Interestingly, HBV-QS-A3 was significantly more prevalent in patients with HCC (80.0%) than in controls (31.9%, P = 4.5 E-7, OR = 11.5, 95% CI: 3.8-38.5). HBV mutation spectra and nucleotide changes were significantly more polymorphic in patients with HCC. Remarkably, HCC patients infected with HBV-QS-A3 were significantly more mutated compared to patients infected with genotype E (P < 0.0001). In addition, G:C>T:A transversions, generally associated with aflatoxin B1 exposure in tropical regions, were significantly more prevalent in HCC patients infected either with HBV-QS-A3 or HBV genotype E (P = 2.2 E-05) when compared to controls. In conclusion, our results indicate that patients infected with HBV-QS-A3 are at increased risk to develop HCC. In addition, viral genomes isolated for patients with tumour are more heavily altered than those found in controls. Preferential targeting of these patients for antiviral treatment is of paramount importance to reduce future HCC incidence in Cameroon.
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Affiliation(s)
- Marie Atsama Amougou
- Centre Pasteur of Cameroon, Yaounde, Cameroon.,Laboratory of Pharmacology and Toxicology of University of Yaounde I, Yaounde, Cameroon
| | - Agnes Marchio
- Unité Organisation nucléaire et Oncogenèse, Institut Pasteur, INSERM U993, Paris, France
| | - Berthold Bivigou-Mboumba
- Unité Mixte de Recherches VIH et Maladies Infectieuses Associées (UMR VIH-MIA), Centre International de Recherches Médicales de Franceville (CIRMF), Libreville, Gabon
| | | | | | | | - Paul Fewou Moundipa
- Laboratory of Pharmacology and Toxicology of University of Yaounde I, Yaounde, Cameroon
| | - Pascal Pineau
- Unité Organisation nucléaire et Oncogenèse, Institut Pasteur, INSERM U993, Paris, France
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Norder H, Twagirumugabe T, Said J, Tian Y, Tang KW, Lindh M. High Frequency of Either Altered Pre-Core StartCodon or Weakened Kozak Sequence in the CorePromoter Region in Hepatitis B Virus A1 Strainsfrom Rwanda. Genes (Basel) 2019; 10:genes10030182. [PMID: 30813638 PMCID: PMC6471190 DOI: 10.3390/genes10030182] [Citation(s) in RCA: 5] [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: 01/28/2019] [Revised: 02/19/2019] [Accepted: 02/20/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.
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Affiliation(s)
- Heléne Norder
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
| | - Theogene Twagirumugabe
- School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
| | - Joanna Said
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
| | - Yarong Tian
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
| | - Ka-Wei Tang
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
| | - Magnus Lindh
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden.
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9
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Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol 2018; 10:807-821. [PMID: 30533182 PMCID: PMC6280160 DOI: 10.4254/wjh.v10.i11.807] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/10/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The severity of hepatic pathology and the response to treatment depend on the hepatitis virus genotype in the infected host. The objective of this review was to determine the distribution of hepatitis virus genotypes in West African countries. A systematic review of the literature in PubMed, Google Scholar and Science Direct was performed to identify 52 relevant articles reporting hepatitis A, B, C, D, E and G viruses genotypes. Hepatitis B virus (HBV) genotype E with a prevalence of 90.6% (95%CI: 0.891-0.920) found in this review, is characterized by low genetic diversity. Hepatitis C virus (HCV) genotypes 1 and 2 represented 96.4% of HCV infections in West African countries, while hepatitis delta virus, hepatitis A virus, hepatitis G virus genotypes 1 and HEV genotype 3 were reported in some studies in Ghana and Nigeria. HBV genotype E is characterized by high prevalence, low genetic diversity and wide geographical distribution. Further studies on the clinical implications of HBV genotype E and HCV genotypes 1 and 2 are needed for the development of an effective treatment against this viral hepatitis in West African countries. Surveillance of the distribution of different genotypes is also needed to reduce recombination rates and prevent the emergence of more virulent viral strains.
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Affiliation(s)
- Maléki Assih
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Abdoul Karim Ouattara
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso.
| | - Birama Diarra
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Albert Theophane Yonli
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Tegwindé Rebeca Compaore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast 00233, Ghana
| | - Florencia Wendkuuni Djigma
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Simplice Karou
- Ecole Supérieure des Techniques Biologiques et Alimentaires (ESTBA-UL), Universite de Lome, Lome 00229, Togo
| | - Jacques Simpore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
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10
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Kostaki EG, Karamitros T, Stefanou G, Mamais I, Angelis K, Hatzakis A, Kramvis A, Paraskevis D. Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach. eLife 2018; 7:36709. [PMID: 30082021 PMCID: PMC6118819 DOI: 10.7554/elife.36709] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 07/28/2018] [Indexed: 12/17/2022] Open
Abstract
Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by the reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.
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Affiliation(s)
- Evangelia-Georgia Kostaki
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Timokratis Karamitros
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
- Department of ZoologyUniversity of OxfordOxfordUnited Kingdom
| | - Garyfallia Stefanou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Ioannis Mamais
- Department of Health Sciences, School of SciencesEuropean University of CyprusNicosiaCyprus
| | - Konstantinos Angelis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, Faculty of Health ScienceUniversity of the WitwatersrandJohannesburgSouth Africa
| | - Dimitrios Paraskevis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
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11
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Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, Dording C, Tarnagda Z, Muller CP, Hübschen JM. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis 2018; 70:15-19. [PMID: 29432880 DOI: 10.1016/j.ijid.2018.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 02/01/2018] [Accepted: 02/02/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES In this study, we monitored the seroprevalence of HBV-HDV co-infection in different population groups in the Western part of Burkina Faso, and described the genetic diversity of the detected virus strains. METHODS Between October 2013 and December 2014, venous blood samples were collected from different cohorts (blood donors, pregnant women, outpatients) in the western region of Burkina Faso. Samples were tested for HBsAg and total anti-HDV antibodies. Positive samples were further analysed for HBV-DNA and HDV-RNA. Genotyping of the detected virus strains was done by nucleotide sequencing and phylogenetic analyses. RESULTS A total of 841 participants were included in this study. The mean age was 27.45 years (range: 7-89 years). HBsAg was found in 117 (13.9%) participants. Of the HBsAg positive samples, 4 (3.4%) were positive for total anti-HDV antibodies and negative for HDV RNA. Phylogenetic analyses based on the HBV complete genome (n=10) and S fragment sequences (n=35) showed that all strains belonged to genotype E. CONCLUSIONS Our study showed a high HBsAg prevalence, but a low rate of HDV co-infection in HBsAg carriers from western Burkina Faso. The predominance of HBV genotype E in the country was confirmed. Our findings contribute to a better understanding of the burden of HBV and HDV infection in western Burkina Faso.
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Affiliation(s)
- Armel M Sanou
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Kenza Benkirane
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
| | - Bachirou Tinto
- Département des Sciences Biomédicales, Laboratoire National de Référence des Fièvres Hémorragiques Virales, Centre Muraz, Bobo-Dioulasso, Burkina Faso.
| | - Assana Cissé
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Tani Sagna
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Abdoul Kader Ilboudo
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Claire Dording
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
| | - Zekiba Tarnagda
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Claude P Muller
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Laboratoire national de santé, 1, rue Louis Rech • L-3555 Dudelange, Luxembourg.
| | - Judith M Hübschen
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
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12
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Virological and Clinical Characteristics of Hepatitis B Virus Genotype A. J Gastroenterol 2018; 53:18-26. [PMID: 28687901 DOI: 10.1007/s00535-017-1367-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 06/30/2017] [Indexed: 02/04/2023]
Abstract
Hepatitis B virus (HBV) infection is one of the most prevalent chronic viral infections in humans. The overall prevalence of hepatitis B surface antigen (HBsAg) is reported to be 3.6%; however, it varies depending upon the geographic area. HBV is classified into ten genotypes (A through J) on the basis of an intergroup genomic divergence of > 8%. Specifically, HBV genotype A exhibits several unique virological and clinical characteristics and can be further classified into seven subtypes. Among them, subtype A2 or Ae (A2/[e]) is occasionally responsible for nosocomial infection and among homosexual males. Regarding virological factors, the G1896A precore mutation is rarely observed in genotype A as it would disrupt an essential stem-loop structure in the ε signal essential for pregenomic RNA packaging. HBV genotype A also harbors a 6-nucleotide C-terminal insertion in the hepatitis B-e antigen (HBeAg) precursor, resulting in a variable-length HBeAg protein product observed in serum of positive patients. These molecular traits likely contribute to the specific clinical presentation of genotype A-infected patients, such as mild acute hepatitis B (AHB), longer persistence of HBsAg positivity in AHB, and increased chronicity after AHB in adults. However, genotype A shows a better response to interferon than other genotypes in chronic hepatitis B patients. Here, we review the virological and clinical characteristics of HBV genotype A that will be useful in elucidating the association among persistent viral infection, host genetic factors, and treatment in future studies.
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13
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Hepatitis B, C and D virus genotypes detected in HBsAg- or anti-HCV-positive people from the Republic of Moldova. Arch Virol 2017; 163:431-438. [PMID: 29119358 DOI: 10.1007/s00705-017-3632-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 10/14/2017] [Indexed: 10/18/2022]
Abstract
In the Republic of Moldova, little is known about hepatitis B, C and D virus (HBV, HCV, HDV) genotypes, although the genetic variant may influence the course and outcome of disease. For HBV genotyping, 301 hepatitis B surface antigen (HBsAg)-positive sera collected in 2010 and 2011 from drug users, prison inmates, commercial sex workers, and the general population in different geographical regions were investigated. The 31 HBsAg-positive sera collected in 2011 were also tested for HDV. Eighty-eight anti-HCV-positive sera collected between 2010 and 2011 from the general population and health care workers were used for HCV genotyping. Phylogenetic analysis of 84 HBV sequences showed that most of the viruses belonged to genotype D (n = 82, 97.6%), predominantly to the subgenotype D1/D2 cluster (n = 75/82, 91.5%). One sequence (74110) clustered as an outlier to this cluster, and six sequences belonged to subgenotype D3. Only two subgenotype A2 sequences were found. Cloning of six samples with ambiguous sequence chromatogram signals showed no mixed infections. Phylogenetic analysis of HCV sequences from 66 patients showed a predominance of subtype 1b (n = 63, 95.5%). Two sequences belonged to subtype 3a, and one to subtype 2a. HDV RNA belonging to genotype 1 was found in two sera (2/31, 6.5%). Thus, genotypes prevalent in Europe were detected for all three hepatitis viruses. For both HBV and HCV, one genotype was dominant, while occasional other variants seem to be restricted to certain cohorts and/or transmission routes.
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14
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Hassan MA, Kim WR, Li R, Smith CI, Fried MW, Sterling RK, Ghany MG, Wahed AS, Ganova-Raeva LM, Roberts LR, Lok ASF. Characteristics of US-Born Versus Foreign-Born Americans of African Descent With Chronic Hepatitis B. Am J Epidemiol 2017; 186:356-366. [PMID: 28525625 DOI: 10.1093/aje/kwx064] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 09/14/2016] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) infection is more common in African Americans than in white Americans. We compared the epidemiologic, clinical, and virological characteristics of US-born African Americans (USAAs) to those of foreign-born African Americans (FBAAs) with chronic hepatitis B. The adult cohort study of the Hepatitis B Research Network enrolls patients with HBV infection from 21 clinical sites in the United States and Canada. A total of 237 (15%) of the adult participants with chronic HBV infection that were enrolled from January 20, 2011, to October 2, 2013, were of African descent, including 57 USAAs and 180 FBAAs (76%). Compared with FBAAs, USAAs were older and more likely to have acquired HBV through sexual exposure, to be HBeAg-positive, to have higher HBV DNA levels, and to be infected with HBV genotype A2. FBAAs from West Africa were more likely to have elevated serum alanine aminotransferase (72% vs. 50%; P < 0.01) and higher HBV DNA levels (median, 3.2 log10 IU/mL vs. 2.8 log10 IU/mL; P = 0.03) compared with East African FBAAs. The predominant HBV genotype among West African FBAAs was E (67%), whereas genotypes A (78%) and D (16%) were common in East African FBAAs. Significant differences were found between USAAs and FBAAs, highlighting the need for tailored strategies for prevention and management of chronic HBV infection for African Americans.
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15
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Lawson-Ananissoh LM, Attia KA, Diallo D, Doffou S, Kissi YH, Bangoura D, Kouamé D, Mahassadi KA, Yao-Bathaix F, Yoman TN. Distribution et implications cliniques des génotypes du virus de l’hépatite B chez 33 porteurs chroniques du virus de l’hépatite B en Côte-d’Ivoire. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s12157-017-0726-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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16
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Hundie GB, Stalin Raj V, Gebre Michael D, Pas SD, Koopmans MP, Osterhaus ADME, Smits SL, Haagmans BL. A novel hepatitis B virus subgenotype D10 circulating in Ethiopia. J Viral Hepat 2017; 24:163-173. [PMID: 27808472 DOI: 10.1111/jvh.12631] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 10/06/2016] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) is genetically highly divergent and classified in ten genotypes and forty subgenotypes in distinct ethno-geographic populations worldwide. Ethiopia is a country with high HBV prevalence; however, little is known about the genetic variability of HBV strains that circulate. Here, we characterize the complete genome of 29 HBV strains originating from five Ethiopian regions, by 454 deep sequencing and Sanger sequencing. Phylogenetically, ten strains were classified as genotype A1 and nineteen as genotype D. Fifteen genotype D strains, provisionally named subgenotype D10, showed a novel distinct cluster supported by high bootstrap value and >4% nucleotide divergence from other known subgenotypes. In addition, the novel D10 strains harboured nine unique amino acid signatures in the surface, polymerase and X genes. Seventy-two per cent of the genotype D strains had the precore premature stop codon G1896A. In addition, 63% genotype A and 33% genotype D strains had the basal core promoter mutations, A1762T/G1764A. Furthermore, four pre-S deletion variants and two recombinants were identified in this study. In conclusion, we identified a novel HBV subgenotype D10 circulating in Ethiopia, underlining the high genetic variability of HBV strains in Africa.
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Affiliation(s)
- G B Hundie
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - V Stalin Raj
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - D Gebre Michael
- National blood bank services, Ministry of Health, Addis Ababa, Ethiopia
| | - S D Pas
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - M P Koopmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - A D M E Osterhaus
- Artemis One health, Utrecht, The Netherlands.,Center for Infection Medicine and Zoonoses Research, University of Veterinary Medicine, Hannover, Germany
| | - S L Smits
- ViroClinics BioScience BV, Rotterdam, The Netherlands
| | - B L Haagmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
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17
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Magoro T, Gachara G, Mavhandu L, Lum E, Kimbi HK, Ndip RN, Bessong P. Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon. Virol J 2016; 13:178. [PMID: 27769271 PMCID: PMC5073451 DOI: 10.1186/s12985-016-0636-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 10/12/2016] [Indexed: 12/19/2022] Open
Abstract
Background HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management. We conducted this study to understand the serologic and genotypic characteristics of HBV among HIV/HBV infected patients in South West and Littoral Regions of Cameroon. Methods Plasma samples were screened for HBsAg, HBeAg, Anti-HBs and anti-HBc using ELISA followed by DNA extraction from all HBsAg positive samples. A 366 bp region covering the overlapping surface/polymerase gene was amplified by a nested PCR and the product sequenced using Big Dye sequencing chemistry. The resulting sequences were then analyzed for genotypes and both escape and drug resistance mutations. Results Of the 455 samples in this study, 25.5 % (n = 116) were HBsAg positive and 46 of these had their DNA successfully amplified. Genotype E was found in 32 samples (69.6 %) and genotype A in the rest of the samples. Escape mutations associated with failure of diagnosis (Y100C, R122K and Q129H) and with vaccine escape (Q129R and T131N) were detected in varying frequencies in the population. Polymerase mutations implicated in resistance to lamivudine and other ʟ-nucleoside analogues were detected in seven patients (15.2 %), while all the samples lacked mutations associated with resistance to adefovir and tenofovir. Conclusions These findings suggest the endemicity of HBV and the predominance of genotypes A and E in the study population. Also, drug resistance findings support the use of tenofovir based ART regimens among HIV/HBV co-infected persons. There is need for continuous HBV screening and monitoring in HIV infected individuals in these regions.
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Affiliation(s)
- Tshifhiwa Magoro
- HIV/AIDS & Global Health Research Program, Department of Microbiology, University of Venda, Private bag X5050, Thohoyandou, 0950, Limpopo, South Africa
| | - George Gachara
- HIV/AIDS & Global Health Research Program, Department of Microbiology, University of Venda, Private bag X5050, Thohoyandou, 0950, Limpopo, South Africa.,Department of Medical Laboratory Sciences, Kenyatta University, Nairobi, Kenya
| | - Lufuno Mavhandu
- HIV/AIDS & Global Health Research Program, Department of Microbiology, University of Venda, Private bag X5050, Thohoyandou, 0950, Limpopo, South Africa
| | - Emmaculate Lum
- Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Buea, Cameroon.,Department of Biological Sciences, Higher Teachers' Training College, University of Yaounde, Yaoundé, Cameroon
| | - Helen K Kimbi
- Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Buea, Cameroon.,Department of Medical Laboratory Science, Faculty of Health Sciences, University of Bamenda, Bamenda, Bambili, Cameroon
| | - Roland N Ndip
- Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Fort Hare, Alice, South Africa.,Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Pascal Bessong
- HIV/AIDS & Global Health Research Program, Department of Microbiology, University of Venda, Private bag X5050, Thohoyandou, 0950, Limpopo, South Africa.
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18
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Angounda BM, Ngouloubi GH, Dzia AB, Boumba LMA, Baha W, Moukassa D, Ahombo G, Ennaji MM, Ibara JR. Molecular characterization of hepatitis B virus among chronic hepatitis B patients from Pointe Noire, Republic of Congo. Infect Agent Cancer 2016; 11:51. [PMID: 27651827 PMCID: PMC5025608 DOI: 10.1186/s13027-016-0088-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Accepted: 06/24/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic Hepatitis B infection is a major health problem in Republic of Congo therefore molecular analysis of HBV strains is important to detect the patients at high risk of disease progression. METHODS Serum samples were obtained from 111 chronic HBV patients in Pointe Noire. HBsAg, HBeAg and HBeAb were detected. A fragment of the preS1 region of HBV was amplified and sequenced to determine genotypes, subgenotypes and to identify mutations. RESULTS Of the 111 samples analyzed, 35 patients were asymptomatic carriers (ASC), 24 with a chronic active hepatitis (CAH), 33 with liver cirrhosis (LC) and 19 have a hepatocellular carcinoma (HCC). The mean age were 45 ± 13 year, 88 (79.3 %) were male and 23 (20.7 %) female. The prevalence of HBeAg was 15.3 % and 73 % of subjects were anti-HBe positive. The mean serum level of alanine aminotransferase transaminase (ALT) and aspartate transaminase (AST) was 25.1 ± 9 IU/L and 28.6 ± 10 IU/L respectively. Eighty two samples out of 111 (73.9 %) were genotyped by the analyzing of the S region of HBV, 58 (70.7 %) cases belonged to HBV genotype E and 24 (29.3 %) were genotype A with three subgenotypes; A3 (66.7 %), A4 (20.8 %) and A6 (12.5 %). Prevalence of genotype A was relatively high in CAH (33.3 %) and HCC (31.6 %) patients in comparison with other groups. The most prevalent amino acids substitutions were R38K found in 14 (17.1 %) sequences, following by H44L in 11 (13.4 %), K13E in 8 (9.8 %), N29K in 8 (9.8 %), A35E in 8 (9.8 %), V80I in 7 (8.5 %) and in 6 (7.3 %) sequences for S90T. Different substitutions located in the hepatocyte binding site were higher among patients with LC and HCC (p < 0.05). CONCLUSIONS This study have shown that HBV genotype E and A were the most frequent strains circulating in Republic of Congo patients. HBV pres1 substitutions found in this study were associated with severe clinical forms of liver diseases. This data have shown the importance of implementing an effective program to fight HBV infection.
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Affiliation(s)
- Brunel Monic Angounda
- Laboratory of screening of the transmitted infectious diseases, National Blood Transfusion Centre, Brazzaville, Republic of Congo
- Cellular and Molecular Biology Laboratory, Faculty of Science and Technology, University Marien NGOUABI, Brazzaville, Congo
- Laboratory of Virology, Microbiology, Quality and Biotechnologies/Eco-toxicology and biodiversity, Virology Team, Cancerology, Quality and Medical Biotechnology, Faculty of Science and Techniques Mohammedia University Hassan II of Casablanca, BP: 146, Mohammedia, 20650 Morocco
| | | | - Amélia Bokilo Dzia
- Laboratory of screening of the transmitted infectious diseases, National Blood Transfusion Centre, Brazzaville, Republic of Congo
- Faculty of Health Sciences, University Marien NGOUABI, Brazzaville, Congo
| | - Luc Magloire Anicet Boumba
- Laboratory of Virology, Microbiology, Quality and Biotechnologies/Eco-toxicology and biodiversity, Virology Team, Cancerology, Quality and Medical Biotechnology, Faculty of Science and Techniques Mohammedia University Hassan II of Casablanca, BP: 146, Mohammedia, 20650 Morocco
- Faculty of Health Sciences, University Marien NGOUABI, Brazzaville, Congo
- General Laondjili Hospital, Pointe-Noire, Congo
| | - Warda Baha
- Laboratory of Virology, Microbiology, Quality and Biotechnologies/Eco-toxicology and biodiversity, Virology Team, Cancerology, Quality and Medical Biotechnology, Faculty of Science and Techniques Mohammedia University Hassan II of Casablanca, BP: 146, Mohammedia, 20650 Morocco
| | - Donatien Moukassa
- Faculty of Health Sciences, University Marien NGOUABI, Brazzaville, Congo
- General Laondjili Hospital, Pointe-Noire, Congo
| | - Gabriel Ahombo
- Cellular and Molecular Biology Laboratory, Faculty of Science and Technology, University Marien NGOUABI, Brazzaville, Congo
| | - Moulay Mustapha Ennaji
- Laboratory of Virology, Microbiology, Quality and Biotechnologies/Eco-toxicology and biodiversity, Virology Team, Cancerology, Quality and Medical Biotechnology, Faculty of Science and Techniques Mohammedia University Hassan II of Casablanca, BP: 146, Mohammedia, 20650 Morocco
| | - Jean-Rosaire Ibara
- Faculty of Health Sciences, University Marien NGOUABI, Brazzaville, Congo
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19
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Candotti D, Diarra B, Bisseye C, Tao I, Pham Quang K, Sanou M, Laperche S, Sanogo R, Allain JP, Simpore J. Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections. J Med Virol 2016; 88:2145-2156. [PMID: 27253483 DOI: 10.1002/jmv.24589] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2016] [Indexed: 12/16/2022]
Abstract
Burkina Faso is a highly endemic area for Hepatitis B virus (HBV) which remains a major challenge for blood safety with >13% of candidate blood donors being chronically infected. However, little is known about the molecular epidemiology of the viral strains currently circulating. In this study, 99 HBV strains from HBsAg positive candidate blood donors in Ougadougou were genetically characterized by sequencing the pre-S/S region of the viral genome. Phylogenetic analyses revealed a 25% prevalence of HBV quasi-subgenotype A3 (A3QS ) co-circulating with the confirmed dominant HBV genotype E (72%). HBV/A3QS sequences formed a sub-cluster closely related to West-African sequences previously characterized, and showed a low intra-group genetic diversity (0.75%) suggesting a relatively recent spreading of HBV/A3QS strains in Burkina Faso. Low genetic diversity of genotype E strains compared to A3QS was confirmed. Mixed infections with the two genotypes were identified in 3% of the donors tested and contributed to artifacts during PCR amplification of the viral genome leading to erroneous apparent intergenotype recombinant sequences. While the co-circulation of two HBV genotypes in a restricted area may favor the emergence of intergenotype recombinant variants, strictly controlled molecular experimental procedures should be used to accurately characterize HBV circulating recombinant forms. J. Med. Virol. 88:2145-2156, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Daniel Candotti
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France. .,Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
| | - Birama Diarra
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Cyrille Bisseye
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso.,Laboratory of Molecular and Cellular Biology, University of Sciences of Masuku, Franceville, Gabon
| | - Issoufou Tao
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Kei Pham Quang
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France
| | - Mahamoudou Sanou
- Unit of Formation in Health Sciences (UFR-SDS), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Syria Laperche
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France
| | - Rokia Sanogo
- Faculty of Pharmacy, University of Engineering Sciences and Technology of Bamako, Bamako, Mali
| | - Jean-Pierre Allain
- Department of Haematology, University of Cambridge, Cambridge, United Kingdom
| | - Jacques Simpore
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
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Cai Q, Zhu H, Zhang Y, Li X, Zhang Z. Hepatitis B virus genotype A: design of reference sequences for sub-genotypes. Virus Genes 2016; 52:325-333. [PMID: 27002608 DOI: 10.1007/s11262-016-1307-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 02/18/2016] [Indexed: 12/29/2022]
Abstract
Genotype A of hepatitis B virus (HBV/A) is widespread and is currently divided into six sub-genotypes. Suitable reference sequences for different sub-genotypes can facilitate research on HBV/A. However, the current reference sequences for this virus are insufficient. In the present work, we retrieved 442 full-length HBV/A genomic sequences from the GenBank database and classified them into sub-genotypes by phylogenetic analysis. By the maximum likelihood method using the MEGA6.0 software, we established the reference sequences for different HBV/A sub-genotypes. Our analyses demonstrated that these reference sequences clustered phylogenetically with known strains, indicating that the reference sequences we established indeed belonged to the right sub-genotypes. HBV/A subtype sequences were selected by geographic origins and grouped as sub-genotypes including A1-South Africa, A2-Europe, A3-Cameroon, and A5-Haiti. Reference sequences of sub-genotypes A1, A2, A3, and A5 were constructed and deposited into GenBank (KP234050-KP234053). By applying phylogenetic analyses, we further determined the time to most recent common ancestor of HBV/A lineages. In conclusion, these newly established reference sequences can provide suitable reference standards for studies on the molecular biology and virology of HBV genotype A.
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Affiliation(s)
- Qun Cai
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, 230022, China
| | - Huilan Zhu
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, 230022, China
| | - Yafei Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, 230022, China
| | - Xu Li
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
| | - Zhenhua Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
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Analysis of hepatitis B virus genotypes by restriction fragment length polymorphism. BIOMEDICA 2015; 36:79-88. [DOI: 10.7705/biomedica.v36i0.2976] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Indexed: 12/15/2022]
Abstract
<p><strong>Introducción.</strong> Se han descrito diez genotipos (A-J) del virus de la hepatitis B (HBV) que están distribuidos en todos los continentes. Una de las técnicas utilizadas para determinar el genotipo viral es el análisis del polimorfismo de longitud de los fragmentos de restricción, un método simple y económico, pero con algunas limitaciones.<br /><strong>Objetivo.</strong> El objetivo inicial del estudio fue identificar el genotipo del HBV mediante RFLP en muestras de suero obtenidas de pacientes y donantes de sangre. Sin embargo, por las discrepancias observadas en los patrones de RFLP fue necesario realizar análisis filogenéticos y un análisis in silico de secuencias del HBV.<br /><strong>Materiales y métodos.</strong> Se obtuvieron 56 muestras de suero. Tras la extracción de ADN, se amplificó un fragmento del ORF S del HBV mediante reacción en cadena de la polimerasa, cuyos productos se analizaron por RFLP con las enzimas <em>AlwI</em>, <em>BsrI</em>, <em>CfrI</em>, <em>HpaII</em> y <em>StyI</em>, y algunos se secuenciaron. Los patrones obtenidos se compararon con los reportados previamente. Se efectuó un análisis<em> in silico</em> de RFLP en consideración de las diferencias entre los patrones esperados y los observados.<br /><strong>Resultados.</strong> Se identificaron los genotipos A y F, subgenotipo F3, en las muestras. Este resultado coincide con lo descrito en estudios previos en los que se ha demostrado que el genotipo F, subgenotipo F3, es prevalente en la población de la región andina del país, en tanto que el genotipo A predomina en el occidente (departamento del Chocó). Con base en el análisis <em>in silico</em> de 229 secuencias virales obtenidas del GenBank y las 11 secuencias de este estudio, se caracterizó un nuevo patrón de RFLP específico para el genotipo F, subgenotipo F3, y se describieron algunas modificaciones en el patrón de RFLP del genotipo A, subgenotipo A1.<br /><strong>Conclusiones.</strong> Se caracterizó el patrón de genotipificación del genotipo F, subgenotipo F3, del HBV mediante RFLP, análisis in silico y secuenciación. Se requieren nuevos análisis in silico con un número mayor de secuencias para validar los patrones de RFLP de los genotipos y subgenotipos del VHB.</p>
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Lopez L, Flichman D, Mojsiejczuk L, Gonzalez MV, Uriarte R, Campos R, Cristina J, Garcia-Aguirre L. Genetic variability of hepatitis B virus in Uruguay: D/F, A/F genotype recombinants. Arch Virol 2015; 160:2209-17. [PMID: 26100402 DOI: 10.1007/s00705-015-2477-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 05/29/2015] [Indexed: 12/22/2022]
Abstract
Hepatitis B virus (HBV) infection is a serious global health problem. Approximately 2 billion people worldwide have been infected, and approximately 350 million individuals currently suffer from HBV-induced chronic liver infection, which causes 600,000 deaths annually from chronic hepatitis, cirrhosis and hepatocellular carcinoma. HBV is classified in eight genotypes (A-H), and two more have been proposed (I-J). In this paper, complete genome sequences of nine Uruguayan HBV are reported. Five samples belong to genotype F1b and one to genotype A2. Three HBV recombinants were detected: A1/F1b, A2/F1b and D3/F1b. The following mutations were detected: a G1896A substitution, a 33-nucleotide deletion from position 2896 to 2928 in the Pre-S1 region involving Pre-S1 residues 3-13, a 33-nt deletion in the Pre-S1 region involving nt 2913-2945 and Pre-S1 residues 9-19. More F genotypes strains than expected were detected in this study, supporting the hypothesis that there are more people of indigenous origin than declared in our population. Also, one third of the samples analyzed were recombinants. This cannot be explained by the low HBV prevalence in Uruguay, but a high HBV infection rate in drug addicts and dialysis patients could act in favor of multiple-genotype HBV infections that could lead to recombination.
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Affiliation(s)
- L Lopez
- Laboratorio de Virología Molecular, Facultad de Ciencias, Centro de Investigaciones Nucleares, Udelar, Montevideo, Uruguay
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Rodríguez Lay LA, Corredor MB, Villalba MC, Frómeta SS, Wong MS, Valdes L, Samada M, Sausy A, Hübschen JM, Muller CP. Genetic Diversity of the Hepatitis B Virus Strains in Cuba: Absence of West-African Genotypes despite the Transatlantic Slave Trade. PLoS One 2015; 10:e0125052. [PMID: 25978398 PMCID: PMC4433336 DOI: 10.1371/journal.pone.0125052] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 03/14/2015] [Indexed: 12/16/2022] Open
Abstract
Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B vaccine. Its population is essentially the result of the population mix of Spanish descendants and former African slaves. Information about genetic characteristics of hepatitis B virus (HBV) strains circulating in the country is scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously absent. All genotype A, D, and C strains exhibited sequence characteristics of the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients showed single, double, or multiple point mutations inside the Major Hydrophilic domain associated with vaccine escape; eighteen (10.5%) patients had mutations in the T-cell epitope (amino acids 28-51), and there were another 111 point mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection. This first genetic study of Cuban HBV viruses revealed only strains that were interspersed with strains from particularly Europe, America, and Asia. The absence of genotype E supports previous hypotheses about an only recent introduction of this genotype into the general population in Africa. The presence of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants strain surveillance to guide vaccination and treatment strategies.
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Affiliation(s)
| | | | | | | | - Meilin S. Wong
- Pedro Kourí Institute of Tropical Medicine, Havana, Cuba
| | - Lidunka Valdes
- Pedro Kourí Institute of Tropical Medicine, Havana, Cuba
| | - Marcia Samada
- Centro de Investigaciones Médico-Quirúrgicas, CIMEQ, Havana, Cuba
| | - Aurélie Sausy
- Laboratory of Immunology, Luxembourg Institute of Health, Esch-Sur- Alzette, Grand-Duchy of Luxembourg
| | - Judith M. Hübschen
- Laboratory of Immunology, Luxembourg Institute of Health, Esch-Sur- Alzette, Grand-Duchy of Luxembourg
| | - Claude P. Muller
- Laboratory of Immunology, Luxembourg Institute of Health, Esch-Sur- Alzette, Grand-Duchy of Luxembourg
- * E-mail:
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Lago BV, Mello FC, Kramvis A, Niel C, Gomes SA. Hepatitis B virus subgenotype A1: evolutionary relationships between Brazilian, African and Asian isolates. PLoS One 2014; 9:e105317. [PMID: 25122004 PMCID: PMC4133366 DOI: 10.1371/journal.pone.0105317] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Accepted: 07/23/2014] [Indexed: 12/13/2022] Open
Abstract
Brazil is a country of low hepatitis B virus (HBV) endemicity in which the genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide sequences of 26 HBV/A isolates, originating from eight Brazilian states, were determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to A2. By phylogenetic analysis, it was shown that all the 23 HBV/A1 isolates clustered together with isolates from Bangladesh, India, Japan, Nepal, the Philippines and United Arab Emirates, but not with those of Congo, Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe. Four amino acid residues in the polymerase (His138 in the terminal protein domain, Pro18 and His90 in the spacer, and Ser109 in the reverse transcriptase), and one (Phe17) in the precore region, predominated in Latin American and Asian HBV/A1 isolates, but were rarely encountered in African isolates, with the exception of those from Somalia. Specific variations of two adjacent amino acids in the C-terminal domain of the HBx protein, namely Ala146 and Pro147, were found in all the Brazilian, but rarely in the other HBV/A1 isolates. By Bayesian analysis, the existence of an 'Asian-American' clade within subgenotype A1 was supported by a posterior probability value of 0.996. The close relatedness of the Brazilian, Asian and Somalian isolates suggests that the HBV/A1 strains predominant in Brazil did not originate from the five million slaves who were imported from Central and Western Africa from 1551 to 1840, but rather from the 300-400,000 captives forcibly removed from southeast Africa at the middle of the 19th century.
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Affiliation(s)
- Bárbara V. Lago
- Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil
| | - Francisco C. Mello
- Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Programme, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Christian Niel
- Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil
| | - Selma A. Gomes
- Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil
- * E-mail:
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Zehender G, Ebranati E, Gabanelli E, Sorrentino C, Lo Presti A, Tanzi E, Ciccozzi M, Galli M. Enigmatic origin of hepatitis B virus: An ancient travelling companion or a recent encounter? World J Gastroenterol 2014; 20:7622-7634. [PMID: 24976700 PMCID: PMC4069291 DOI: 10.3748/wjg.v20.i24.7622] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/08/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes, particularly those concerning the origin and dispersion histories of genotypes A, D, E and F and their subgenotypes. The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain. It is hypothesised that HBV evolutionary rates are time dependent, and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.
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Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol 2014; 20:7152-68. [PMID: 24966586 PMCID: PMC4064061 DOI: 10.3748/wjg.v20.i23.7152] [Citation(s) in RCA: 146] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 11/28/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
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Andernach IE, Hunewald OE, Muller CP. Bayesian inference of the evolution of HBV/E. PLoS One 2013; 8:e81690. [PMID: 24312336 PMCID: PMC3843692 DOI: 10.1371/journal.pone.0081690] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Accepted: 10/21/2013] [Indexed: 12/16/2022] Open
Abstract
Despite its wide spread and high prevalence in sub-Saharan Africa, hepatitis B virus genotype E (HBV/E) has a surprisingly low genetic diversity, indicating an only recent emergence of this genotype in the general African population. Here, we performed extensive phylogeographic analyses, including Bayesian MCMC modeling. Our results indicate a mutation rate of 1.9×10−4 substitutions per site and year (s/s/y) and confirm a recent emergence of HBV/E, most likely within the last 130 years, and only after the transatlantic slave-trade had come to an end. Our analyses suggest that HBV/E originated from the area of Nigeria, before rapidly spreading throughout sub-Saharan Africa. Interestingly, viral strains found in Haiti seem to be the result of multiple introductions only in the second half of the 20th century, corroborating an absence of a significant number of HBV/E strains in West Africa several centuries ago. Our results confirm that the hyperendemicity of HBV(E) in today's Africa is a recent phenomenon and likely the result of dramatic changes in the routes of viral transmission in a relatively recent past.
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Affiliation(s)
- Iris E. Andernach
- Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg
| | - Oliver E. Hunewald
- Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg
| | - Claude P. Muller
- Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg
- * E-mail:
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Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, Khudyakov YE. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. J Clin Virol 2013; 58:59-66. [PMID: 23871163 PMCID: PMC4591023 DOI: 10.1016/j.jcv.2013.06.028] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Revised: 05/23/2013] [Accepted: 06/21/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). STUDY DESIGN/RESULTS Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape. CONCLUSIONS The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.
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Affiliation(s)
- Joseph C Forbi
- Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333, USA.
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29
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Brichler S, Lagathu G, Chekaraou MA, Le Gal F, Edouard A, Dény P, Césaire R, Gordien E. African, Amerindian and European hepatitis B virus strains circulate on the Caribbean Island of Martinique. J Gen Virol 2013; 94:2318-2329. [PMID: 23884366 DOI: 10.1099/vir.0.055459-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have been described in well-characterized ethnogeographical populations. Martinique has been at a crossroads between Africa, Europe, India and the Americas because of the slave trade (17th-19th centuries), followed by an important immigration of Indian and West African workers. In this work, we aimed to study the molecular epidemiology of HBV infection in Martinique according to this unique settlement pattern. To that end, blood samples from 86 consecutive HBV-infected patients from the main hospitals of the island, were retrospectively analysed. Direct sequencing of the pre-S1 or pre-C-C region or complete genome sequencing, followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1 (68.6 %), HBV/A2 (10.5 %), HBV/D, mainly HBV/D3 and HBV/D4 (8.1 %), HBV/F (3.5 %), and also HBV/E (2.3 %), two strains isolated from two West-African patients. Moreover, 74 % of the HBeAg-negative strains harboured classical pre-C-C mutations, and most HBV/A1 strains also containing specific mutations. Finally, various patterns of deletion mutants in pre-S and pre-C-C regions were found. In conclusion, our findings point to historical and migration-related issues in HBV-genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from Africa during the slave trade, and further supporting the hypothesis that HBV/E has emerged recently in West Africa (<150 years). Potential origins of 'European' HBV/A2 and HBV/D3, 'Amerindian' HBV/F, and HBV/D4 strains are also discussed. Such HBV genetic diversity, beyond its epidemiological interest, may have a clinical impact on the natural history of HBV infection in Martinique.
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Affiliation(s)
- Ségolène Brichler
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Gisèle Lagathu
- Service de Bactériologie, Virologie du Centre Hospitalier Régional et Universitaire de Rennes, Pontchaillou, France
| | - Mariama Abdou Chekaraou
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Frédéric Le Gal
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - André Edouard
- Service d'Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique, France
| | - Paul Dény
- Centre de Recherche sur le Cancer, Équipe 16, INSERM U1052, CNRS UMR 5286, Lyon, France.,Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Raymond Césaire
- Laboratoire de Virologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique; EA 4537, Université Antilles-Guyane, France
| | - Emmanuel Gordien
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
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30
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Alvarado-Mora MV, Pinho JRR. Distribution of HBV genotypes in Latin America. Antivir Ther 2013; 18:459-65. [PMID: 23792558 DOI: 10.3851/imp2599] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2012] [Indexed: 02/07/2023]
Abstract
Approximately 2 billion people worldwide are infected with HBV, and 350 million people are chronic carriers. HBV is classified into nine genotypes (A to I). Genotype F is the most prevalent in the Spanish-speaking countries and in the Amerindian population in South America. HBV genotype F was primarily found in indigenous populations from South America and is divided into four subgenotypes (F1 to F4). Subgenotype F1 is further divided into F1a (found in Costa Rica and El Salvador) and F1b (found in in Alaska, Argentina and Chile). Subgenotypes F2 and F3 cocirculate in the north of South America: F2a is found in Brazil and Venezuela, F2b is described only in Venezuela, F3 is frequent in Colombia, Venezuela and Panama, and F4 is reported from the central and south areas of South America, including Bolivia, Argentina and southern Brazil. HBV genotypes and subgenotypes have distinct geographical distributions. It is currently under discussion whether they are associated with different prognoses, considering the patterns of severity of liver diseases in various populations. Furthermore, global human migrations affect the pattern of genotype distribution, introducing genotypes differing from those found in the original inhabitants.
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Affiliation(s)
- Mónica V Alvarado-Mora
- Laboratory of Tropical Gastroenterology and Hepatology 'João Alves de Queiroz and Castorina Bittencourt Alves', Institute of Tropical Medicine, Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil.
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Hepatitis B virus subgenotyping: history, effects of recombination, misclassifications, and corrections. INFECTION GENETICS AND EVOLUTION 2013; 16:355-61. [PMID: 23538336 DOI: 10.1016/j.meegid.2013.03.021] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 03/15/2013] [Accepted: 03/16/2013] [Indexed: 12/23/2022]
Abstract
Hepatitis B virus (HBV) has evolved into phylogenetically separable genotypes and subgenotypes. Accurately assigning the subgenotype for an HBV strain is of clinical and epidemiological significance. In this paper, we review the recommendations currently employed for HBV subgenotyping, the history of HBV subgenotyping, the effects of recombination on HBV subgenotyping, misclassifications in HBV subgenotyping, and suggestions are made to correct the misclassifications. Finally, proposals are made to guide future HBV subgenotyping.
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Alvarado-Mora MV, Romano CM, Gomes-Gouvêa MS, Gutierrez MF, Carrilho FJ, Pinho JRR. Phylogenetic analysis of complete genome sequences of hepatitis B virus from an Afro-Colombian community: presence of HBV F3/A1 recombinant strain. Virol J 2012; 9:244. [PMID: 23092209 PMCID: PMC3499267 DOI: 10.1186/1743-422x-9-244] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Accepted: 10/22/2012] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is one of the most prevalent viral infections in humans and represents a serious public health problem. In Colombia, our group reported recently the presence of subgenotypes F3, A2 and genotype G in Bogotá. The aim of this study was to characterize the HBV genotypes circulating in Quibdó, the largest Afro-descendant community in Colombia. Sixty HBsAg-positive samples were studied. A fragment of 1306 bp (S/POL) was amplified by nested PCR. Positive samples to S/POL fragment were submitted to PCR amplification of the HBV complete genome. FINDINGS The distribution of HBV genotypes was: A1 (52.17%), E (39.13%), D3 (4.3%) and F3/A1 (4.3%). An HBV recombinant strain subgenotype F3/A1 was found for the first time. CONCLUSIONS This study is the first analysis of complete HBV genome sequences from Afro-Colombian population. It was found an important presence of HBV/A1 and HBV/E genotypes. A new recombinant strain of HBV genotype F3/A1 was reported in this population. This fact may be correlated with the introduction of these genotypes in the times of slavery.
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Affiliation(s)
- Mónica V Alvarado-Mora
- Laboratory of Gastroenterology and Hepatology, São Paulo Institute of Tropical Medicine and Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil.
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Shi W, Zhu C, Zheng W, Carr MJ, Higgins DG, Zhang Z. Subgenotype reclassification of genotype B hepatitis B virus. BMC Gastroenterol 2012; 12:116. [PMID: 22925657 PMCID: PMC3523008 DOI: 10.1186/1471-230x-12-116] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2012] [Accepted: 08/24/2012] [Indexed: 02/06/2023] Open
Abstract
Background Nine subgenotypes from genotype B have been identified for hepatitis B virus (HBV). However, these subgenotypes were less conclusive as they were often designated based on a few representative strains. In addition, subgenotype B6 was designated twice for viruses of different origin. Methods All complete genome sequences of genotype B HBV were phylogenetically analyzed. Sequence divergences between different potential subgenotypes were also assessed. Results Both phylogenetic and sequence divergence analyses supported the designation of subgenotypes B1, B2, B4, and B6 (from Arctic). However, sequence divergences between previously designated B3, B5, B7, B8, B9 and another B6 (from China) were mostly less than 4%. In addition, subgenotype B3 did not form a monophyly. Conclusion Current evidence failed to classify original B5, B7, B8, B9, and B6 (from China) as subgenotypes. Instead, they could be considered as a quasi-subgenotype B3 of Southeast Asian and Chinese origin. In addition, previously designated B6 (from Arctic) should be renamed as B5 for continuous numbering. This novel classification is well supported by both the phylogeny and sequence divergence of > 4%.
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Affiliation(s)
- Weifeng Shi
- Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Nansha, 511458, Guangzhou, China.
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Abstract
Hepatitis B virus (HBV) is a hepatotropic DNA virus. The HBV genome is prone to variations. Based on genomic variations, HBV is divided into ten genotypes, many subgenotypes and quasispecies. These genotypes, subgenotypes and quasispecies have distinct race and geographic distribution and have been associated with outcome of HBV infection, disease progression and treatment.
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Shi W, Carr MJ, Dunford L, Zhu C, Hall WW, Higgins DG. Identification of novel inter-genotypic recombinants of human hepatitis B viruses by large-scale phylogenetic analysis. Virology 2012; 427:51-9. [PMID: 22374235 DOI: 10.1016/j.virol.2012.01.030] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2011] [Revised: 01/14/2012] [Accepted: 01/26/2012] [Indexed: 02/08/2023]
Abstract
Recombination plays an important role in the evolutionary history of Hepatitis B virus (HBV). We performed a phylogenetic analysis of 3403 full-length HBV genome sequences isolated from humans to define the genotype. The genome sequences were divided into 13 sub-datasets, each approximately 250 bp in length. Genotype designations obtained from the sub-datasets that differed from the genotype defined by the whole genome were assigned as putative recombinants. Our results showed that 3379 out of 3403 sequences belonged to the previously described and putative genotypes A to J respectively, with 315 sequences defined in this analysis. The remaining 24 viruses had sequence divergence of less than 8% with both genotypes B and C and were provisionally assigned genotype "BC". 1047 out of 3403 sequences were identified to be putative recombinants, of which 72 were identified to be novel recombinants. Notably, all viruses of the herein described genotype "BC" were identified to be B/C recombinants.
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Affiliation(s)
- Weifeng Shi
- The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
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Santos AO, Alvarado-Mora MV, Botelho L, Vieira DS, Pinho JRR, Carrilho FJ, Honda ER, Salcedo JM. Characterization of hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil. Virol J 2010; 7:315. [PMID: 21073730 PMCID: PMC2994811 DOI: 10.1186/1743-422x-7-315] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2010] [Accepted: 11/12/2010] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) can be classified into nine genotypes (A-I) defined by sequence divergence of more than 8% based on the complete genome. This study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive patients from Rondônia, Brazil. A fragment of 1306 bp partially comprising surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was purified and sequenced. Amplified DNA was purified and sequenced on an ABI PRISM® 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were aligned with reference sequences obtained from the GenBank using Clustal X software and then edited with Se-Al software. Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC) approach using BEAST v.1.5.3. RESULTS The subgenotypes distribution was A1 (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). CONCLUSIONS These results for the first HBV genotypic characterization in Rondônia state are consistent with other studies in Brazil, showing the presence of several HBV genotypes that reflects the mixed origin of the population, involving descendants from Native Americans, Europeans, and Africans.
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Affiliation(s)
- Alcione O Santos
- Research Center for Tropical Medicine--CEPEM/Tropical Pathology Research Institute-IPEPATRO. Porto Velho, RO, Brazil
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