1. The HIV-1 proviral landscape reveals Nef contributes to HIV-1 persistence in effector memory CD4+ T-cells
- Author
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Duette, Gabriel, Hiener, Bonnie, Morgan, Hannah, Mazur, Fernando G, Mathivanan, Vennila, Horsburgh, Bethany A, Fisher, Katie, Tong, Orion, Lee, Eunok, Ahn, Haelee, Shaik, Ansari, Fromentin, Rémi, Hoh, Rebecca, Bacchus-Souffan, Charline, Nasr, Najla, Cunningham, Anthony, Hunt, Peter W, Chomont, Nicolas, Turville, Stuart G, Deeks, Steven G, Kelleher, Anthony D, Schlub, Timothy E, and Palmer, Sarah
- Subjects
HIV/AIDS ,Infectious Diseases ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,CD4-Positive T-Lymphocytes ,DNA ,Viral ,HIV Infections ,HIV-1 ,Humans ,Proviruses ,Viral Load ,nef Gene Products ,Human Immunodeficiency Virus ,AIDS/HIV ,Adaptive immunity ,Infectious disease ,Molecular genetics ,T cells ,Medical and Health Sciences ,Immunology - Abstract
Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4+ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4+ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4+ T cells when compared with naive, central, and transitional memory CD4+ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.
- Published
- 2022