Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen

Author:

Neuner-Jehle NadiaORCID,Zeeb Marius,Thorball Christian W.,Fellay Jacques,Metzner Karin J.,Frischknecht Paul,Neumann Kathrin,Leeman Christine,Rauch Andri,Stöckle Marcel,Huber Michael,Perreau Matthieu,Bernasconi Enos,Notter Julia,Hoffmann Matthias,Leuzinger Karoline,Günthard Huldrych F.,Pasin Chloé,Kouyos Roger D.ORCID,

Abstract

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis.

Funder

Swiss National Science Foundation

Swiss HIV Cohort Study

SHCS research foundation

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Yvonne-Jacob Foundation

University of Zurich

Collegium Helveticum

Publisher

Public Library of Science (PLoS)

Reference63 articles.

1. The factors associated with natural disease progression from HIV to AIDS in the absence of ART, a propensity score matching analysis;XC Jia;Epidemiology and Infection,2020

2. Predictors of disease progression in HIV infection: a review;SE Langford;AIDS Research and Therapy,2007

3. Host genetic variation and HIV disease: from mapping to mechanism;V Naranbhai;Immunogenetics,2017

4. HIV and HLA class I: an evolving relationship;PJ Goulder;Immunity,2012

5. HLA antigens associated with susceptibility/resistance to HIV-1 infection;C Rohowsky-Kochan;Hum Immunol,1998

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