The influence of human genetic variation on Epstein-Barr virus sequence diversity
The influence of human genetic variation on Epstein-Barr virus sequence diversity
Abstract Epstein-Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4+ T cell count <200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.
R¨1eger Sina、Swiss HIV Cohort Study、Lawless Dylan、G¨1nthard Huldrych F.、Rauch Andri、Zdobnov Evgeny、Fellay Jacques、Khanna Nina、Naret Olivier、Morfopoulou Sofia、Kahlert Christian R.、McLaren Paul J、Breuer Judith、Loetscher Alexis、Bernasconi Enos、Hammer Christian、Cavassini Matthias、Depledge Daniel P.
School of Life Sciences||Swiss Institute of BioinformaticsSchool of Life Sciences||Swiss Institute of BioinformaticsDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich||Institute of Medical Virology, University of Zurich, ZurichDepartment of Infectious Diseases, Bern University Hospital, University of BernSwiss Institute of Bioinformatics||Department of Genetic Medicine and Development, University of Geneva Medical SchoolSchool of Life Sciences||Swiss Institute of Bioinformatics||Precision Medicine Unit, Lausanne University Hospital and University of LausanneDepartment of Infectious Diseases and Hospital Epidemiology and Department of Biomedicine, University and University Hospital of BaselSchool of Life Sciences||Swiss Institute of BioinformaticsDivision of Infection and Immunity, University College LondonDivision of Infectious Diseases, Cantonal Hospital of St. GallenJC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada||Department of Medical Microbiology and Infectious Diseases, University of ManitobaDivision of Infection and Immunity, University College LondonSwiss Institute of Bioinformatics||Department of Genetic Medicine and Development, University of Geneva Medical SchoolDivision of Infectious Diseases, Regional Hospital of LuganoGenentech IncService of Infectious Diseases, Lausanne University Hospital and University of LausanneDivision of Infection and Immunity, University College London
基础医学遗传学分子生物学
R¨1eger Sina,Swiss HIV Cohort Study,Lawless Dylan,G¨1nthard Huldrych F.,Rauch Andri,Zdobnov Evgeny,Fellay Jacques,Khanna Nina,Naret Olivier,Morfopoulou Sofia,Kahlert Christian R.,McLaren Paul J,Breuer Judith,Loetscher Alexis,Bernasconi Enos,Hammer Christian,Cavassini Matthias,Depledge Daniel P..The influence of human genetic variation on Epstein-Barr virus sequence diversity[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2020.12.02.20242370.点此复制
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