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The HIV-1 latent reservoir is largely sensitive to circulating T cells
- Warren, Joanna A;
- Zhou, Shuntai;
- Xu, Yinyan;
- Moeser, Matthew J;
- MacMillan, Daniel R;
- Council, Olivia;
- Kirchherr, Jennifer;
- Sung, Julia M;
- Roan, Nadia;
- Adimora, Adaora A;
- Joseph, Sarah;
- Kuruc, JoAnn D;
- Gay, Cynthia L;
- Margolis, David M;
- Archin, Nancie;
- Brumme, Zabrina L;
- Swanstrom, Ronald;
- Goonetilleke, Nilu
Abstract
HIV-1-specific CD8+ T cells are an important component of HIV-1 curative strategies. Viral variants in the HIV-1 reservoir may limit the capacity of T cells to detect and clear virus-infected cells. We investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 (PLWH) durably suppressed on antiretroviral therapy (ART). We identified all reactive T cell epitopes in the HIV-1 proteome for each participant and sequenced HIV-1 outgrowth viruses from resting CD4+ T cells. All non-synonymous mutations in reactive T cell epitopes were tested for their effect on the size of the T cell response, with a≥50% loss defined as an escape mutation. The majority (68%) of T cell epitopes harbored no detectable escape mutations. These findings suggest that circulating T cells in PLWH on ART could contribute to control of rebound and could be targeted for boosting in curative strategies.
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