Zobrazit v EDS

Joint host-pathogen genomic analysis identifies hepatitis B virus mutations associated with human NTCP and HLA class I variation

Uloženo v:
Podrobná bibliografie
Název: Joint host-pathogen genomic analysis identifies hepatitis B virus mutations associated with human NTCP and HLA class I variation
Autoři: Zhi Ming Xu, Gnimah Eva Gnouamozi, Sina Rüeger, Patrick R. Shea, Maria Buti, Henry LY. Chan, Patrick Marcellin, Dylan Lawless, Olivier Naret, Matthias Zeller, Arne Schneuing, Andreas Scheck, Thomas Junier, Darius Moradpour, Ondrej Podlaha, Vithika Suri, Anuj Gaggar, Mani Subramanian, Bruno Correia, David Gfeller, Stephan Urban, Jacques Fellay
Přispěvatelé: Institut Català de la Salut, [Xu ZM, Rüeger S] School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Swiss Institute of Bioinformatics, Lausanne, Switzerland. [Gnouamozi GE] Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany. [Shea PR] Institute for Genomic Medicine, Columbia University, New York, NY, USA. [Buti M] Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBEREHD del Instituto Carlos III, Barcelona, Spain. [Chan HLY] The Chinese University of Hong Kong, Hong Kong, China, Vall d'Hebron Barcelona Hospital Campus
Zdroj: Am J Hum Genet
Scientia
Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname
American journal of human genetics, vol. 111, no. 6, pp. 1018-1034
Informace o vydavateli: Elsevier BV, 2024.
Rok vydání: 2024
Témata: Hepatitis B virus, Other subheadings::Other subheadings::Other subheadings::/genetics, FENÓMENOS Y PROCESOS::fenómenos genéticos::estructuras genéticas::genoma::genoma microbiano::genoma viral, PHENOMENA AND PROCESSES::Microbiological Phenomena::Host-Pathogen Interactions, Virus de l'hepatitis B - Aspectes genètics, Epitopes, T-Lymphocyte, Organic Anion Transporters, Sodium-Dependent, Genome, Viral, Article, Hepatitis B, Chronic, Microorganismes patògens, ORGANISMOS::virus::virus ADN::Hepadnaviridae::Orthohepadnavirus::virus de la hepatitis B, Otros calificadores::Otros calificadores::Otros calificadores::/genética, Humans, Hepatitis B virus/genetics, Organic Anion Transporters, Sodium-Dependent/genetics, Organic Anion Transporters, Sodium-Dependent/metabolism, Symporters/genetics, Symporters/metabolism, Mutation, Host-Pathogen Interactions/genetics, Host-Pathogen Interactions/immunology, Hepatitis B, Chronic/virology, Hepatitis B, Chronic/genetics, Hepatitis B Surface Antigens/genetics, Epitopes, T-Lymphocyte/genetics, Epitopes, T-Lymphocyte/immunology, Genomics/methods, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/metabolism, HBV entry, escape variants, evolutionary genomics, hepatitis B virus, host-pathogen genomics, immunogenetics, selection, viral restriction, ORGANISMS::Viruses::DNA Viruses::Hepadnaviridae::Orthohepadnavirus::Hepatitis B virus, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación, Hepatitis B Surface Antigens, Symporters, Histocompatibility Antigens Class I, Genomes bacterians, Genomics, 3. Good health, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Structures::Genome::Genome, Microbial::Genome, Viral, Anomalies cromosòmiques, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation, FENÓMENOS Y PROCESOS::fenómenos microbiológicos::interacciones huésped-patógeno, Host-Pathogen Interactions
Popis: Evolutionary changes in the hepatitis B virus (HBV) genome could reflect its adaptation to host-induced selective pressure. Leveraging paired human exome and ultra-deep HBV genome-sequencing data from 567 affected individuals with chronic hepatitis B, we comprehensively searched for the signatures of this evolutionary process by conducting "genome-to-genome" association tests between all human genetic variants and viral mutations. We identified significant associations between an East Asian-specific missense variant in the gene encoding the HBV entry receptor NTCP (rs2296651, NTCP S267F) and mutations within the receptor-binding region of HBV preS1. Through in silico modeling and in vitro preS1-NTCP binding assays, we observed that the associated HBV mutations are in proximity to the NTCP variant when bound and together partially increase binding affinity to NTCP S267F. Furthermore, we identified significant associations between HLA-A variation and viral mutations in HLA-A-restricted T cell epitopes. We used in silico binding prediction tools to evaluate the impact of the associated HBV mutations on HLA presentation and observed that mutations that result in weaker binding affinities to their cognate HLA alleles were enriched. Overall, our results suggest the emergence of HBV escape mutations that might alter the interaction between HBV PreS1 and its cellular receptor NTCP during viral entry into hepatocytes and confirm the role of HLA class I restriction in inducing HBV epitope variations.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 0002-9297
DOI: 10.1016/j.ajhg.2024.04.013
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38749427
https://hdl.handle.net/11351/11578
https://serval.unil.ch/resource/serval:BIB_9CF13B4886CA.P001/REF.pdf
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_9CF13B4886CA4
https://serval.unil.ch/notice/serval:BIB_9CF13B4886CA
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....5cd6a516b7b06616e4220eb0ec84a9a5
Databáze: OpenAIRE
Popis
Abstrakt:Evolutionary changes in the hepatitis B virus (HBV) genome could reflect its adaptation to host-induced selective pressure. Leveraging paired human exome and ultra-deep HBV genome-sequencing data from 567 affected individuals with chronic hepatitis B, we comprehensively searched for the signatures of this evolutionary process by conducting "genome-to-genome" association tests between all human genetic variants and viral mutations. We identified significant associations between an East Asian-specific missense variant in the gene encoding the HBV entry receptor NTCP (rs2296651, NTCP S267F) and mutations within the receptor-binding region of HBV preS1. Through in silico modeling and in vitro preS1-NTCP binding assays, we observed that the associated HBV mutations are in proximity to the NTCP variant when bound and together partially increase binding affinity to NTCP S267F. Furthermore, we identified significant associations between HLA-A variation and viral mutations in HLA-A-restricted T cell epitopes. We used in silico binding prediction tools to evaluate the impact of the associated HBV mutations on HLA presentation and observed that mutations that result in weaker binding affinities to their cognate HLA alleles were enriched. Overall, our results suggest the emergence of HBV escape mutations that might alter the interaction between HBV PreS1 and its cellular receptor NTCP during viral entry into hepatocytes and confirm the role of HLA class I restriction in inducing HBV epitope variations.
ISSN:00029297
DOI:10.1016/j.ajhg.2024.04.013