Journal Article

The HIV-1 proviral landscape reveals that Nef contributes to HIV- 1 persistence in effector memory CD4+ T cells

Bacchus-Souffan, Charline, Hunt, Peter W, Tong, Orion, Deeks, Steven G, Kelleher, Anthony D, Hiener, Bonnie, Fisher, Katie, Shaik, Ansari, Fromentin, Rémi, Chomont, Nicolas, Mathivanan, Vennila, Nasr, Najla, Cunningham, Anthony L, Palmer, Sarah, Lee, Eunok, Turville, Stuart G, Duette, Gabriel, Horsburgh, Bethany A, Ahn, Haelee, Schlub, Timothy E, Morgan, Hannah, Mazur, Fernando G, Hoh, Rebecca

2022

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Antiretroviral drugs / Antiretroviral therapy / Biomedical research / CD4 antigen / Drug therapy / Effector cells / Gene expression / HIV / Human immunodeficiency virus / Immunological memory / Infections / Lymphocytes / Lymphocytes T / Memory cells / Mutation / Proteins / Proviruses / Therapeutic targets