Author:
Rüeger Sina,Hammer Christian,Loetscher Alexis,McLaren Paul J.,Lawless Dylan,Naret Olivier,Khanna Nina,Bernasconi Enos,Cavassini Matthias,Günthard Huldrych F.,Kahlert Christian R.,Rauch Andri,Depledge Daniel P.,Morfopoulou Sofia,Breuer Judith,Zdobnov Evgeny,Fellay Jacques,Aebi-Popp Karoline,Anagnostopoulos Alexia,Battegay Manuel,Bernasconi Enos,Böni Jürg,Braun Dominique,Bucher Heiner,Calmy Alexandra,Cavassini Matthias,Ciuffi Angela,Dollenmaier Guenter,Egger Matthias,Elzi Luigia,Fehr Jan,Fellay Jacques,Furrer Hansjakob,Fux Christoph,Günthard Huldrych F.,Haerry David,Hasse Barbara,Hirsch Hans,Hoffmann Matthias,Hösli Irene,Huber Michael,Kahlert Christian R.,Kaiser Laurent,Keiser Olivia,Klimkait Thomas,Kottanattu Lisa,Kouyos Roger,Kovari Helen,Ledergerber Bruno,Martinetti Gladys,de Tejada Begoña Martinez,Marzolini Catia,Metzner Karin,Müller Nicolas,Nicca Dunja,Paioni Paolo,Pantaleo Giuseppe,Perreau Matthieu,Rauch Andri,Rudin Christoph,Scherrer Alexandra,Schmid Patrick,Speck Roberto,Stöckle Marcel,Tarr Philip,Trkola Alexandra,Vernazza Pietro,Wagner Noémie,Wandeler Gilles,Weber Rainer,Yerly Sabine,
Abstract
AbstractEpstein–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.
Funder
Fondation Leenaards
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Swiss HIV Cohort Research Foundation
Publisher
Springer Science and Business Media LLC