HIV-1 variants are archived throughout infection and persist in the reservoir

Autoři: Kelsie Brooks aff001;  Bradley R. Jones aff002;  Dario A. Dilernia aff001;  Daniel J. Wilkins aff001;  Daniel T. Claiborne aff001;  Samantha McInally aff001;  Jill Gilmour aff003;  William Kilembe aff004;  Jeffrey B. Joy aff002;  Susan A. Allen aff004;  Zabrina L. Brumme aff002;  Eric Hunter aff001
Působiště autorů: Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America aff001;  British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada aff002;  Human Immunology Lab, International AIDS Vaccine Initiative, London, England, United Kingdom aff003;  Zambia-Emory HIV Research Project, Lusaka, Zambia aff004;  Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada aff005;  Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America aff006;  Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada aff007
Vyšlo v časopise: HIV-1 variants are archived throughout infection and persist in the reservoir. PLoS Pathog 16(6): e32767. doi:10.1371/journal.ppat.1008378
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008378


The HIV-1 reservoir consists of latently infected cells that persist despite antiretroviral therapy (ART). Elucidating the proviral genetic composition of the reservoir, particularly in the context of pre-therapy viral diversity, is therefore important to understanding reservoir formation and the persistence of latently infected cells. Here we investigate reservoir proviral variants from 13 Zambian acutely-infected individuals with additional pre-therapy sampling for a unique comparison to the ART-naïve quasispecies. We identified complete transmitted/founder (TF) viruses from seroconversion plasma samples, and additionally amplified and sequenced HIV-1 from plasma obtained one year post-infection and just prior to ART initiation. While the majority of proviral variants in the reservoir were most closely related to viral variants from the latest pre-therapy time point, we also identified reservoir proviral variants dating to or near the time of infection, and to intermediate time points between infection and treatment initiation. Reservoir proviral variants differing by five or fewer nucleotide changes from the TF virus persisted during treatment in five individuals, including proviral variants that exactly matched the TF in two individuals, one of whom had remained ART-naïve for more than six years. Proviral variants during treatment were significantly less divergent from the TF virus than plasma variants present at the last ART-naïve time point. These findings indicate that reservoir proviral variants are archived throughout infection, recapitulating much of the viral diversity that arises throughout untreated HIV-1 infection, and strategies to target and reduce the reservoir must therefore permit for the clearance of proviruses encompassing this extensive diversity.

Klíčová slova:

Antiretroviral therapy – HIV – HIV-1 – Phylogenetic analysis – Phylogenetics – Polymerase chain reaction – Sequence analysis – Viral replication


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