Barcoded HIV-1 reveals viral persistence driven by clonal proliferation and distinct epigenetic patterns.

ABSTRACT: The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring HIV cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays of latently infected cells. This study utilizes barcoded HIV to analyze the reservoir in humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes and 504 proviral barcodes linked to 15,305 integration sites at the single RNA or DNA molecule in vivo. We track viral genetic diversity throughout early infection, ART, and rebound. The proviral reservoir retains genetic diversity despite cellular clonal proliferation and viral seeding by rebounding virus. Non-prolifer

SUBMITTER: Zhang TH 

PROVIDER: S-EPMC11829055 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature