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

Autor: Nadia Neuner-Jehle, Marius Zeeb, Christian W Thorball, Jacques Fellay, Karin J Metzner, Paul Frischknecht, Kathrin Neumann, Christine Leeman, Andri Rauch, Marcel Stöckle, Michael Huber, Matthieu Perreau, Enos Bernasconi, Julia Notter, Matthias Hoffmann, Karoline Leuzinger, Huldrych F Günthard, Chloé Pasin, Roger D Kouyos, Swiss HIV Cohort Study (SHCS)
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Pathogens, Vol 20, Iss 8, p e1012385 (2024)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1012385
Popis: 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.
Databáze: Directory of Open Access Journals
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