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For: Ligat G, Cazal R, Hantz S, Alain S. The human cytomegalovirus terminase complex as an antiviral target: a close-up view. FEMS Microbiol Rev 2018;42:137-145. [PMID: 29361041 PMCID: PMC5972660 DOI: 10.1093/femsre/fuy004] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 01/17/2018] [Indexed: 01/13/2023] Open

For:	Ligat G, Cazal R, Hantz S, Alain S. The human cytomegalovirus terminase complex as an antiviral target: a close-up view. FEMS Microbiol Rev 2018;42:137-145. [PMID: 29361041 PMCID: PMC5972660 DOI: 10.1093/femsre/fuy004] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 01/17/2018] [Indexed: 01/13/2023] Open

Number

Cited by Other Article(s)

Staliunaite L, Puhach O, Ostermann E, Rosenke K, Nichols J, Oestereich L, Sogoba N, Feldmann H, Davison AJ, Jarvis MA, Brune W. Molecular cloning and host range analysis of three cytomegaloviruses from Mastomys natalensis. J Virol 2025;99:e0214724. [PMID: 40202317 PMCID: PMC12090778 DOI: 10.1128/jvi.02147-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/14/2025] [Indexed: 04/10/2025] Open

Abstract

Herpesvirus-based vectors are attractive for use as conventional or transmissible vaccines against emerging zoonoses in inaccessible animal populations. In both cases, cytomegaloviruses (CMVs) as members of the subfamily Betaherpesvirinae are particularly suitable for vaccine development as they are highly specific for their natural host species, infect a large proportion of their host population, and cause mild infections in healthy individuals. The Natal multimammate mouse (Mastomys natalensis) is the natural reservoir of Lassa virus, which causes deadly hemorrhagic fever in humans. M. natalensis was recently reported to harbor at least three different cytomegaloviruses (MnatCMV1, MnatCMV2, and MnatCMV3). Herein, we report the molecular cloning of three complete MnatCMV genomes in a yeast and bacterial artificial chromosome (YAC-BAC) hybrid vector. Purified viral genomes were cloned in yeast by single-step transformation-associated recombination (STAR cloning) and subsequently transferred to Escherichia coli for further genetic manipulation. The integrity of the complete cloned viral genomes was verified by sequencing, and the replication fitness of viruses reconstituted from these clones was analyzed by replication kinetics in M. natalensis fibroblasts and kidney epithelial cells. We also found that neither parental nor cloned MnatCMVs replicated in mouse and rat fibroblasts, nor did they show sustained replication in baby hamster kidney cells, consistent with the expected narrow host range for these viruses. We further demonstrated that an exogenous sequence can be inserted by BAC-based mutagenesis between open reading frames M25 and m25.1 of MnatCMV2 without affecting replication fitness in vitro, identifying this site as potentially suitable for the insertion of vaccine target antigen genes.IMPORTANCECytomegaloviruses (CMVs) recently discovered in the Natal multimammate mouse (Mastomys natalensis) are widespread within the M. natalensis population. Since these rodents also serve as natural hosts of the human pathogen Lassa virus (LASV), we investigated the potential suitability of M. natalensis CMVs (MnatCMVs) as vaccine vectors. We describe the cloning of three different MnatCMV genomes as bacterial artificial chromosomes (BACs). The replicative capacity and species specificity of these BAC-derived MnatCMVs were analyzed in multiple cell types. We also identified a transgene insertion site within one of the MnatCMV genomes suitable for the incorporation of vaccine target antigens. Together, this study provides a foundation for the development of MnatCMVs as transmissible MnatCMV-based LASV vaccines to reduce LASV prevalence in hard-to-reach M. natalensis populations and, thereby, zoonotic transmission to humans.

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Harmening S, Bogdanow B, Wagner K, Liu F, Messerle M, Borst EM. Interaction of human cytomegalovirus pUL52 with major components of the viral DNA encapsidation network underlines its essential role in genome cleavage-packaging. J Virol 2025;99:e0220124. [PMID: 40062846 PMCID: PMC11998523 DOI: 10.1128/jvi.02201-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 02/12/2025] [Indexed: 04/16/2025] Open

Abstract

Cleavage of human cytomegalovirus (HCMV) genomes and their packaging into capsids requires at least seven essential viral proteins, yet it is not completely understood how these proteins cooperate to accomplish this task. Besides the portal protein pUL104 and the terminase subunits pUL51, pUL56, and pUL89, the UL52 protein is also necessary for HCMV genome encapsidation; however, knowledge about pUL52 is scant. In the absence of pUL52, viral concatemers are not cleaved into unit-length genomes and no DNA-filled capsids are observed, yet no viral or cellular proteins interacting with pUL52 have been identified that would explain how pUL52 exerts its essential role in the HCMV infection cycle. In this study, we aimed at a comprehensive definition of pUL52-interacting proteins in infected cells. Using suitable HCMV mutants, we employed three complementary state-of-the-art proteomic approaches, namely biotin ligase-dependent proximity labeling, affinity purification, and cross-linking mass spectrometry. These experiments, combined with thorough validation by immunoblotting, pointed to several viral DNA-associated proteins and key players pivotal for genome encapsidation as interactors of pUL52. The most noticeable direct pUL52 interaction partners were the terminase subunits pUL56 and pUL89 as well as the portal protein pUL104. Hence, we suggest a model of pUL52 function in which pUL52 mediates association of HCMV genomes with the terminase subunits and the capsid portal. Taken together, our data contribute to the understanding of an essential viral process previously recognized as a prominent antiviral target. Disturbing the identified pUL52 interactions may provide a starting point to develop novel antiviral medication.

IMPORTANCE

Human cytomegalovirus (HCMV) can evoke severe disease in immunocompromised patients and, moreover, is the most frequent viral cause of malformations in newborns. The virus-specific process of genome cleavage and packaging into capsids has emerged as an Achilles heel in the HCMV life cycle, which can be targeted by novel antiviral drugs, yet the mechanism of viral DNA encapsidation is only partially understood. Here, we report that the essential viral cleavage-packaging protein pUL52 interacts with several HCMV proteins known to be crucial for genome packaging, with the most prominent ones being the terminase complex and the portal protein. These data provide insight into the role of pUL52 during HCMV infection and may lay the basis for the development of additional antiviral substances tackling viral DNA packaging.

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Nanamiya H, Tanaka D, Hiyama G, Isogai T, Watanabe S. Detection of four isomers of the human cytomegalovirus genome using nanopore long-read sequencing. Virus Genes 2024;60:377-384. [PMID: 38861195 DOI: 10.1007/s11262-024-02083-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 06/01/2024] [Indexed: 06/12/2024]

Saltiel G, Faure E, Assaf A, Chopin MC, Moreau F, Faure K, Goeminne C, Vuotto F. Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients. Clin Transplant 2024;38:e15327. [PMID: 38686437 DOI: 10.1111/ctr.15327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 05/02/2024]

Abstract

INTRODUCTION

Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR).

METHODS

In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen.

RESULTS

The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir.

CONCLUSION

This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

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Monday LM, Keri V, Chandrasekar PH. Advances in pharmacotherapies for cytomegalovirus infection: what is the current state of play? Expert Opin Pharmacother 2024;25:685-694. [PMID: 38717943 DOI: 10.1080/14656566.2024.2353627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/07/2024] [Indexed: 06/12/2024]

Piret J, Boivin G. Management of Cytomegalovirus Infections in the Era of the Novel Antiviral Players, Letermovir and Maribavir. Infect Dis Rep 2024;16:65-82. [PMID: 38247977 PMCID: PMC10801527 DOI: 10.3390/idr16010005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/08/2024] [Accepted: 01/12/2024] [Indexed: 01/23/2024] Open

Menéndez-Arias L, Gago F. Antiviral Agents: Structural Basis of Action and Rational Design. Subcell Biochem 2024;105:745-784. [PMID: 39738962 DOI: 10.1007/978-3-031-65187-8_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]

Gourin C, Alain S, Hantz S. Anti-CMV therapy, what next? A systematic review. Front Microbiol 2023;14:1321116. [PMID: 38053548 PMCID: PMC10694278 DOI: 10.3389/fmicb.2023.1321116] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/06/2023] [Indexed: 12/07/2023] Open

Abstract

Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs available to treat HCMV infection, targeting viral polymerase, whose use is complicated by toxicity and the emergence of resistance. Maribavir and letermovir are the latest antivirals to have been developed with other targets. The approval of letermovir represents an important innovation for CMV prevention in hematopoietic stem cell transplant recipients, whereas maribavir allowed improving the management of refractory or resistant infections in transplant recipients. However, in case of multidrug resistance or for the prevention and treatment of congenital CMV infection, finding new antivirals or molecules able to inhibit CMV replication with the lowest toxicity remains a critical need. This review presents a range of molecules known to be effective against HCMV. Molecules with a direct action against HCMV include brincidofovir, cyclopropavir and anti-terminase benzimidazole analogs. Artemisinin derivatives, quercetin and baicalein, and anti-cyclooxygenase-2 are derived from natural molecules and are generally used for different indications. Although they have demonstrated indirect anti-CMV activity, few clinical studies were performed with these compounds. Immunomodulating molecules such as leflunomide and everolimus have also demonstrated indirect antiviral activity against HCMV and could be an interesting complement to antiviral therapy. The efficacy of anti-CMV immunoglobulins are discussed in CMV congenital infection and in association with direct antiviral therapy in heart transplanted patients. All molecules are described, with their mode of action against HCMV, preclinical tests, clinical studies and possible resistance. All these molecules have shown anti-HCMV potential as monotherapy or in combination with others. These new approaches could be interesting to validate in clinical trials.

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Nho D, Lee R, Cho SY, Lee DG, Kim EJ, Park S, Lee SE, Cho BS, Kim YJ, Lee S, Kim HJ. Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation under 100-Day Letermovir Prophylaxis: A Real-World 1-Year Follow-Up Study. Viruses 2023;15:1884. [PMID: 37766290 PMCID: PMC10536589 DOI: 10.3390/v15091884] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open

Affiliation(s)

Dukhee Nho Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (D.N.); (R.L.); (D.-G.L.) Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Raeseok Lee Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (D.N.); (R.L.); (D.-G.L.) Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Sung-Yeon Cho Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (D.N.); (R.L.); (D.-G.L.) Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Dong-Gun Lee Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (D.N.); (R.L.); (D.-G.L.) Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Eun-Jin Kim Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Silvia Park Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Sung-Eun Lee Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Byung-Sik Cho Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Yoo-Jin Kim Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Seok Lee Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)
Hee-Je Kim Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (E.-J.K.); (S.P.); (S.-E.L.); (B.-S.C.); (Y.-J.K.); (S.L.); (H.-J.K.)

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Recio V, González I, Tarragó D. Cytomegalovirus drug resistance mutations in transplant recipients with suspected resistance. Virol J 2023;20:153. [PMID: 37464399 PMCID: PMC10355059 DOI: 10.1186/s12985-023-02127-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 07/11/2023] [Indexed: 07/20/2023] Open

Panda K, Parashar D, Viswanathan R. An Update on Current Antiviral Strategies to Combat Human Cytomegalovirus Infection. Viruses 2023;15:1358. [PMID: 37376657 PMCID: PMC10303229 DOI: 10.3390/v15061358] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 05/29/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open

Almehmadi M, Haq IU, Alsaiari AA, Alshabrmi FM, Abdulaziz O, Allahyani M, Aladhadh M, Shafie A, Aljuaid A, Alotaibi RT, Ullah J, Alharthi NS. Identification of Small Molecule Inhibitors of Human Cytomegalovirus pUL89 Endonuclease Using Integrated Computational Approaches. Molecules 2023;28:3938. [PMID: 37175348 PMCID: PMC10180037 DOI: 10.3390/molecules28093938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/28/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023] Open

Perchetti GA, Biernacki MA, Xie H, Castor J, Joncas-Schronce L, Ueda Oshima M, Kim Y, Jerome KR, Sandmaier BM, Martin PJ, Boeckh M, Greninger AL, Zamora D. Cytomegalovirus breakthrough and resistance during letermovir prophylaxis. Bone Marrow Transplant 2023;58:430-436. [PMID: 36693927 DOI: 10.1038/s41409-023-01920-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 01/08/2023] [Accepted: 01/12/2023] [Indexed: 01/26/2023]

Affiliation(s)

Garrett A Perchetti Department of Laboratory Medicine and Pathology, University of Washington, School of Medicine, Seattle, WA, USA
Melinda A Biernacki Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Hu Xie Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Jared Castor Department of Laboratory Medicine and Pathology, University of Washington, School of Medicine, Seattle, WA, USA
Laurel Joncas-Schronce Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Masumi Ueda Oshima Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA Division of Medical Oncology, Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA
YoungJun Kim Department of Pathology, University of Virginia, School of Medicine, Charlottesville, VA, USA
Keith R Jerome Department of Laboratory Medicine and Pathology, University of Washington, School of Medicine, Seattle, WA, USA Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Brenda M Sandmaier Division of Medical Oncology, Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Paul J Martin Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Michael Boeckh Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA
Alexander L Greninger Department of Laboratory Medicine and Pathology, University of Washington, School of Medicine, Seattle, WA, USA Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Danniel Zamora Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.

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Zhang J, Kamoi K, Zong Y, Yang M, Ohno-Matsui K. Cytomegalovirus Anterior Uveitis: Clinical Manifestations, Diagnosis, Treatment, and Immunological Mechanisms. Viruses 2023;15:185. [PMID: 36680225 PMCID: PMC9867175 DOI: 10.3390/v15010185] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/05/2023] [Accepted: 01/06/2023] [Indexed: 01/10/2023] Open

Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections. Trop Med Infect Dis 2022;7:tropicalmed7120439. [PMID: 36548694 PMCID: PMC9784992 DOI: 10.3390/tropicalmed7120439] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 11/30/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open

Abstract

Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated.

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Kotton CN, Torre-Cisneros J, Aguado JM, Alain S, Baldanti F, Baumann G, Boeken U, de la Calle M, Carbone J, Ciceri F, Comoli P, Couzi L, Danziger-Isakov L, Fernández-Ruiz M, Girmenia C, Grossi PA, Hirsch HH, Humar A, Kamar N, Kotton C, Ljungman P, Malagola M, Mira E, Mueller N, Sester M, Teng CLJ, Torre-Cisneros J, Ussetti P, Westall G, Wolf D, Zamora M. Cytomegalovirus in the transplant setting: Where are we now and what happens next? A report from the International CMV Symposium 2021. Transpl Infect Dis 2022;24:e13977. [PMID: 36271650 PMCID: PMC10078482 DOI: 10.1111/tid.13977] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 09/16/2022] [Accepted: 09/27/2022] [Indexed: 12/24/2022]

Affiliation(s)

Camille N Kotton Transplant and Immunocompromised Host Infectious Diseases, Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Julián Torre-Cisneros Maimónides Institute for Biomedical Research of Cordoba (IMIBIC)/Reina Sofía University Hospital/University of Cordoba (UCO), Cordoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain

José Maria Aguado University Hospital 12 de Octubre, CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
Sophie Alain French References Center for Herpes Viruses, Microbiology Department, CHU-Limoges, Limoges, France
Fausto Baldanti Università di Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Gabriele Baumann Landeskrankenhaus Steyr, Steyr, Austria
Udo Boeken Department of Cardiac Surgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany
Maria de la Calle La Paz Hospital, Madrid, Spain
Javier Carbone Hospital General Universitario Gregorio Marañón, Madrid, Spain
Fabio Ciceri IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milan, Italy
Patrizia Comoli Cell Factory and Center for Advanced Therapies and Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Lionel Couzi Department of Nephrology, Transplantation, Dialysis and Apheresis, CHU Bordeaux CNRS-UMR 5164 ImmunoConcEpT, Bordeaux University, Bordeaux, France
Lara Danziger-Isakov Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, USA
Mario Fernández-Ruiz University Hospital 12 de Octubre, Madrid, Spain
Corrado Girmenia AOU Policlinico Umberto I, Rome, Italy
Paolo Antonio Grossi Università degli Studi dell'Insubria - ASST SetteLaghi, Varese, Italy
Hans H Hirsch University Hospital Basel, Basel, Switzerland
Atul Humar University of Toronto, Toronto, Canada
Nassim Kamar Toulouse University Hospital, Toulouse, France
Camille Kotton Massachusetts General Hospital, Boston, USA
Per Ljungman Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
Michele Malagola University of Brescia, Brescia, Italy
Estefania Mira Reina Sofía University Hospital, Cordoba, Spain
Nicolas Mueller Universitäts Spital Zürich, Zürich, Switzerland
Martina Sester Universität des Saarlandes, Homburg, Germany
Chieh-Lin Jerry Teng Taichung Veterans General Hospital, Taichung, Taiwan
Julian Torre-Cisneros Reina Sofía University Hospital, Cordoba, Spain
Piedad Ussetti Hospital Puerta de Hierro Majadahonda, Madrid, Spain
Glen Westall Alfred Hospital, Melboune, Australia
Dana Wolf Hadassah University Medical Center, Jerusalem, Israel
Marty Zamora University of Colorado at Denver Anschutz Medical Center, Colorado, USA

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He T, Edwards TC, Majima R, Jung E, Kankanala J, Xie J, Geraghty RJ, Wang Z. Repurposing N-hydroxy thienopyrimidine-2,4-diones (HtPD) as inhibitors of human cytomegalovirus pUL89 endonuclease: Synthesis and biological characterization. Bioorg Chem 2022;129:106198. [PMID: 36265353 PMCID: PMC9643671 DOI: 10.1016/j.bioorg.2022.106198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/03/2022] [Accepted: 10/05/2022] [Indexed: 11/02/2022]

Turner DL, Mathias RA. The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction. Front Cell Dev Biol 2022;10:1053139. [PMID: 36506089 PMCID: PMC9732275 DOI: 10.3389/fcell.2022.1053139] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 11/10/2022] [Indexed: 11/27/2022] Open

Jung E, Majima R, Edwards TC, Soto‐Acosta R, Geraghty RJ, Wang Z. 8-Hydroxy-1,6-naphthyridine-7-carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease. ChemMedChem 2022;17:e202200334. [PMID: 35879245 PMCID: PMC9463105 DOI: 10.1002/cmdc.202200334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Indexed: 11/10/2022]

Weinberger S, Steininger C. Reliable quantification of Cytomegalovirus DNAemia in Letermovir treated patients. Antiviral Res 2022;201:105299. [PMID: 35354065 DOI: 10.1016/j.antiviral.2022.105299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/21/2022] [Accepted: 03/23/2022] [Indexed: 11/28/2022]

He T, Edwards TC, Xie J, Aihara H, Geraghty RJ, Wang Z. 4,5-Dihydroxypyrimidine Methyl Carboxylates, Carboxylic Acids, and Carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease. J Med Chem 2022;65:5830-5849. [PMID: 35377638 PMCID: PMC9441020 DOI: 10.1021/acs.jmedchem.2c00203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

Wrapp D, Ye X, Ku Z, Su H, Jones HG, Wang N, Mishra AK, Freed DC, Li F, Tang A, Li L, Jaijyan DK, Zhu H, Wang D, Fu TM, Zhang N, An Z, McLellan JS. Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies. SCIENCE ADVANCES 2022;8:eabm2546. [PMID: 35275718 PMCID: PMC8916728 DOI: 10.1126/sciadv.abm2546] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]

Affiliation(s)

Daniel Wrapp Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Xiaohua Ye Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Zhiqiang Ku Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Hang Su Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Harrison G. Jones Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Nianshuang Wang Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Akaash K. Mishra Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Daniel C. Freed Merck Research Laboratories, Merck & Co. Inc., Kenilworth, NJ 07033, USA
Fengsheng Li Merck Research Laboratories, Merck & Co. Inc., Kenilworth, NJ 07033, USA
Aimin Tang Merck Research Laboratories, Merck & Co. Inc., Kenilworth, NJ 07033, USA
Leike Li Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Dabbu Kumar Jaijyan Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
Hua Zhu Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
Dai Wang Merck Research Laboratories, Merck & Co. Inc., Kenilworth, NJ 07033, USA
Tong-Ming Fu Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Ningyan Zhang Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Zhiqiang An Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA Corresponding author. (Z.A.); (J.S.M.)
Jason S. McLellan Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA Corresponding author. (Z.A.); (J.S.M.)

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Two-Metal Ion-Dependent Enzymes as Potential Antiviral Targets in Human Herpesviruses. mBio 2022;13:e0322621. [PMID: 35073739 PMCID: PMC8787488 DOI: 10.1128/mbio.03226-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open

Abstract

The majority of drug discovery efforts against herpesviruses have focused on nucleoside analogs that target viral DNA polymerases, agents that are associated with dose-limiting toxicity and/or a narrow spectrum of activity. We are pursuing a strategy based on targeting two-metal ion-dependent (TMID) viral enzymes. This family of enzymes consists of structurally related proteins that share common active sites containing conserved carboxylates predicted to coordinate divalent cations essential for catalysis. Compounds that target TMID enzymes, such as HIV integrase and influenza endoribonuclease, have been successfully developed for clinical use. HIV integrase inhibitors have been reported to inhibit replication of herpes simplex virus (HSV) and other herpesviruses; however, the molecular targets of their antiviral activities have not been identified. We employed a candidate-based approach utilizing several two-metal-directed chemotypes and the potential viral TMID enzymatic targets in an effort to correlate target-based activity with antiviral potency. The panel of compounds tested included integrase inhibitors, the anti-influenza agent baloxavir, three natural products previously shown to exhibit anti-HSV activity, and two 8-hydroxyquinolines (8-HQs), AK-157 and AK-166, from our in-house program. The integrase inhibitors exhibited weak overall anti-HSV-1 activity, while the 8-HQs were shown to inhibit both HSV-1 and cytomegalovirus (CMV). Target-based analysis demonstrated that none of the antiviral compounds acted by inhibiting ICP8, contradicting previous reports. On the other hand, baloxavir inhibited the proofreading exonuclease of HSV polymerase, while AK-157 and AK-166 inhibited the alkaline exonuclease UL12. In addition, AK-157 also inhibited the catalytic activity of the HSV polymerase, which provides an opportunity to potentially develop dual-targeting agents against herpesviruses. IMPORTANCE Human herpesviruses (HHVs) establish lifelong latent infections, which undergo periodic reactivation and remain a major cause of morbidity and mortality, especially in immunocompromised individuals. Currently, HHV infections are treated primarily with agents that target viral DNA polymerase, including nucleoside analogs; however, long-term treatment can be complicated by the development of drug resistance. New therapies with novel modes of action would be important not only for the treatment of resistant viruses but also for use in combination therapy to reduce dose-limiting toxicities and potentially eliminate infection. Since many essential HHV proteins are well conserved, inhibitors of novel targets would ideally exhibit broad-spectrum activity against multiple HHVs.

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The Synthesis and Anti-Cytomegalovirus Activity of Piperidine-4-Carboxamides. Viruses 2022;14:v14020234. [PMID: 35215828 PMCID: PMC8876412 DOI: 10.3390/v14020234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/19/2022] [Accepted: 01/21/2022] [Indexed: 01/04/2023] Open

Abstract

Treatment options for human cytomegalovirus (CMV) remain limited and are associated with significant adverse effects and the selection of resistant CMV strains in transplant recipients and congenitally infected infants. Although most approved drugs target and inhibit the CMV DNA polymerase, additional agents with distinct mechanisms of action are needed for the treatment and prevention of CMV. In a large high throughput screen using our CMV-luciferase reporter Towne, we identified several unique inhibitors of CMV replication. Here, we synthesize and test in vitro 13 analogs of the original NCGC2955 hit (1). Analogs with no activity against the CMV-luciferase at 10 µM and 30 µM (2–6, 10–14) were removed from further analysis. Three analogs (7–9) inhibited CMV replication in infected human foreskin fibroblasts. The EC₅₀ of (1) was 1.7 ± 0.6 µM and 1.99 ± 0.15 µM, based on luciferase and plaque assay, respectively. Compounds 7, 8, and 9 showed similar activities: the EC₅₀ values of 7 were 0.21 ± 0.06 µM (luciferase) and 0.55 ± 0.06 (plaque), of 8: 0.28 ± 0.06 µM and 0.42 ± 0.07, and of 9: 0.30 ± 0.05 µM (luciferase) and 0.35 ± 0.07 (plaque). The CC₅₀ for 7, 8, and 9 in non-infected human foreskin fibroblasts was > 500µM, yielding a selectivity index of >1500. Compounds 1, 7, and 8 were also tested in CMV-infected primary human hepatocytes and showed a dose–response against CMV by luciferase activity and viral protein expression. None of the active compounds inhibited herpes simplex virus 1 or 2. Compounds 7 and 8 inhibited mouse CMV replication in vitro. Both inhibited CMV at late stages of replication; 7 reduced virus yield at all late time points, although not to the same degree as letermovir. Finally, the activity of analog 8 was additive with newly identified CMV inhibitors (MLS8969, NFU1827, MSL8554, and MSL8091) and with ganciclovir. Further structural activity development should provide promising anti-CMV agents for use in clinical studies.

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Gupta M, Manek G, Dombrowski K, Maiwall R. Newer developments in viral hepatitis: Looking beyond hepatotropic viruses. World J Meta-Anal 2021;9:522-542. [DOI: 10.13105/wjma.v9.i6.522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/09/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open

Cytomegalovirus Infections in Children with Primary and Secondary Immune Deficiencies. Viruses 2021;13:v13102001. [PMID: 34696432 PMCID: PMC8538792 DOI: 10.3390/v13102001] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/30/2021] [Accepted: 10/02/2021] [Indexed: 12/15/2022] Open

Draganova EB, Valentin J, Heldwein EE. The Ins and Outs of Herpesviral Capsids: Divergent Structures and Assembly Mechanisms across the Three Subfamilies. Viruses 2021;13:v13101913. [PMID: 34696343 PMCID: PMC8539031 DOI: 10.3390/v13101913] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 09/18/2021] [Accepted: 09/20/2021] [Indexed: 12/17/2022] Open

Ligat G, Alain S, Hantz S. Towards a Prophylactic Vaccine for the Prevention of HCMV Infection. Vaccines (Basel) 2021;9:vaccines9090968. [PMID: 34579205 PMCID: PMC8472991 DOI: 10.3390/vaccines9090968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 08/28/2021] [Indexed: 11/21/2022] Open

Muller C, Alain S, Gourin C, Baumert TF, Ligat G, Hantz S. New Insights into Human Cytomegalovirus pUL52 Structure. Viruses 2021;13:v13081638. [PMID: 34452502 PMCID: PMC8402748 DOI: 10.3390/v13081638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/02/2021] [Accepted: 08/14/2021] [Indexed: 10/31/2022] Open

Metal binding 6-arylthio-3-hydroxypyrimidine-2,4-diones inhibited human cytomegalovirus by targeting the pUL89 endonuclease of the terminase complex. Eur J Med Chem 2021;222:113640. [PMID: 34147908 DOI: 10.1016/j.ejmech.2021.113640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 12/18/2022]

Recent studies of nitrogen containing heterocyclic compounds as novel antiviral agents: A review. Bioorg Chem 2021;114:105076. [PMID: 34157555 DOI: 10.1016/j.bioorg.2021.105076] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 05/13/2021] [Accepted: 06/07/2021] [Indexed: 12/14/2022]

Successful Use of Heterologous CMV-Reactive T Lymphocyte to Treat Severe Refractory Cytomegalovirus (CMV) Infection in a Liver Transplanted Patient: Correlation of the Host Antiviral Immune Reconstitution with CMV Viral Load and CMV miRNome. Microorganisms 2021;9:microorganisms9040684. [PMID: 33810329 PMCID: PMC8066103 DOI: 10.3390/microorganisms9040684] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/16/2022] Open

Muller C, Alain S, Baumert TF, Ligat G, Hantz S. Structures and Divergent Mechanisms in Capsid Maturation and Stabilization Following Genome Packaging of Human Cytomegalovirus and Herpesviruses. Life (Basel) 2021;11:life11020150. [PMID: 33669389 PMCID: PMC7920273 DOI: 10.3390/life11020150] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/11/2021] [Accepted: 02/12/2021] [Indexed: 01/13/2023] Open

Didychuk AL, Gates SN, Gardner MR, Strong LM, Martin A, Glaunsinger BA. A pentameric protein ring with novel architecture is required for herpesviral packaging. eLife 2021;10:e62261. [PMID: 33554858 PMCID: PMC7889075 DOI: 10.7554/elife.62261] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 02/05/2021] [Indexed: 02/06/2023] Open

Jo H, Kwon DE, Han SH, Min SY, Hong YM, Lim BJ, Lee KH, Jo JH. De Novo Genotypic Heterogeneity in the UL56 Region in Cytomegalovirus-Infected Tissues: Implications for Primary Letermovir Resistance. J Infect Dis 2021;221:1480-1487. [PMID: 31802131 DOI: 10.1093/infdis/jiz642] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 12/04/2019] [Indexed: 01/07/2023] Open

Schubert L, Fisecker L, Thalhammer F, Burgmann H, Steininger C. Letermovir for the compassionate therapeutic use of cytomegalovirus infection. Eur J Clin Microbiol Infect Dis 2021;40:435-439. [PMID: 32914220 PMCID: PMC7817558 DOI: 10.1007/s10096-020-03990-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/15/2020] [Indexed: 12/23/2022]

Li G, Jing X, Zhang P, De Clercq E. Antiviral Classification. ENCYCLOPEDIA OF VIROLOGY 2021. [PMCID: PMC7917465 DOI: 10.1016/b978-0-12-814515-9.00126-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]

Njue A, Coyne C, Margulis AV, Wang D, Marks MA, Russell K, Das R, Sinha A. The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms. Viruses 2020;13:v13010020. [PMID: 33374185 PMCID: PMC7823935 DOI: 10.3390/v13010020] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/14/2020] [Accepted: 12/21/2020] [Indexed: 12/14/2022] Open

Lee SM, Han D, Kwon M, Noh H, Lee JH, Yoon Y, Cho JY, Ahn JH, Yoon K. Gamma secretase inhibition impairs HCMV replication by reduction of immediate early gene expression at the transcriptional level. Antiviral Res 2020;183:104867. [PMID: 32755660 DOI: 10.1016/j.antiviral.2020.104867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 11/24/2022]

Figueiredo CG, Luchs A, Durigon EL, de Oliveira DBL, da Silva VB, Mello RM, Afonso AMS, de Oliveira MI. Frequency of congenital cytomegalovirus infections in newborns in the Sao Paulo State, 2010-2018. Rev Inst Med Trop Sao Paulo 2020;62:e54. [PMID: 32756824 PMCID: PMC7458071 DOI: 10.1590/s1678-9946202062054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 07/14/2020] [Indexed: 12/01/2022] Open

Jentzer A, Veyrard P, Roblin X, Saint-Sardos P, Rochereau N, Paul S, Bourlet T, Pozzetto B, Pillet S. Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms 2020;8:1078. [PMID: 32698383 PMCID: PMC7409252 DOI: 10.3390/microorganisms8071078] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/10/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022] Open

Affiliation(s)

Alexandre Jentzer GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
Pauline Veyrard GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
Xavier Roblin GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
Pierre Saint-Sardos Laboratory of Bacteriology, University Hospital of Clermont-Ferrand, 63100 Clermont-Ferrand, France;
Nicolas Rochereau GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
Stéphane Paul GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
Thomas Bourlet GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
Bruno Pozzetto GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
Sylvie Pillet GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.) Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France

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Wang YQ, Zhao XY. Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules. Front Microbiol 2020;11:1511. [PMID: 32765441 PMCID: PMC7378892 DOI: 10.3389/fmicb.2020.01511] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/10/2020] [Indexed: 12/12/2022] Open

Translation of the long-term fundamental studies on viral DNA packaging motors into nanotechnology and nanomedicine. SCIENCE CHINA-LIFE SCIENCES 2020;63:1103-1129. [DOI: 10.1007/s11427-020-1752-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/04/2020] [Indexed: 02/07/2023]

Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020;46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]

Ligat G, Muller C, Alain S, Hantz S. [The terminase complex, a relevant target for the treatment of HCMV infection]. Med Sci (Paris) 2020;36:367-375. [PMID: 32356713 DOI: 10.1051/medsci/2020063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open

Koepf US, Klehr HU, Eis-Huebinger AM, Aldabbagh S, Strassburg CP, Boes D, Lutz P. Suppression of CMV Infection with Letermovir in a Kidney Transplant Patient. Eur J Case Rep Intern Med 2020;7:001622. [PMID: 32665929 PMCID: PMC7350956 DOI: 10.12890/2020_001622] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 03/11/2020] [Indexed: 11/05/2022] Open

Perales MA, Papanicolaou GA. Cytomegalovirus Viremia and Death After Hematopoietic Cell Transplantation: More Complex Than "To Have and Have Not"? Clin Infect Dis 2020;70:1534-1535. [PMID: 31179483 PMCID: PMC7346759 DOI: 10.1093/cid/ciz492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 06/06/2019] [Indexed: 11/12/2022] Open

Ye L, Qian Y, Yu W, Guo G, Wang H, Xue X. Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review. Front Microbiol 2020;11:2104. [PMID: 33013768 PMCID: PMC7498621 DOI: 10.3389/fmicb.2020.02104] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 08/10/2020] [Indexed: 12/18/2022] Open

Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication. Viruses 2019;11:v11121093. [PMID: 31779110 PMCID: PMC6950143 DOI: 10.3390/v11121093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/21/2019] [Accepted: 11/22/2019] [Indexed: 02/05/2023] Open

Brissot E, Alsuliman T, Beauvais D, Bonnin A, Mear JB, Souchet L, Villate A, Yakoub-Agha I, Bazarbachi A. [Antiviral prophylaxis for CMV, HSV/VZV and HBV in allogeneic hematopoietic cell transplantation in adult patients: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Bull Cancer 2019;107:S1-S6. [PMID: 31627903 DOI: 10.1016/j.bulcan.2019.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/14/2019] [Accepted: 09/04/2019] [Indexed: 02/08/2023]