1. The HIV-1 latent reservoir is largely sensitive to circulating T cells
- Author
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Joanna A Warren, Shuntai Zhou, Yinyan Xu, Matthew J Moeser, Daniel R MacMillan, Olivia Council, Jennifer Kirchherr, Julia M Sung, Nadia R Roan, Adaora A Adimora, Sarah Joseph, JoAnn D Kuruc, Cynthia L Gay, David M Margolis, Nancie Archin, Zabrina L Brumme, Ronald Swanstrom, and Nilu Goonetilleke
- Subjects
HIV ,CD8 ,T cell ,hiv cure ,hiv reservoir ,Medicine ,Science ,Biology (General) ,QH301-705.5 - 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.
- Published
- 2020
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