The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.
The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.
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DOI：
10.1172/jci154422
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发表时间：
2022-04-01
期刊：
影响因子：
--
通讯作者：
Palmer S
中科院分区：
文献类型：
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作者：
Duette G;Hiener B;Morgan H;Mazur FG;Mathivanan V;Horsburgh BA;Fisher K;Tong O;Lee E;Ahn H;Shaik A;Fromentin R;Hoh R;Bacchus-Souffan C;Nasr N;Cunningham AL;Hunt PW;Chomont N;Turville SG;Deeks SG;Kelleher AD;Schlub TE;Palmer S
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.
