HIV-1 Genomes Are Enriched in Memory CD4 <sup>+</sup> T-Cells with Short Half-Lives
Vincent Morcilla, Charline Bacchus-Souffan, Katie Fisher, Bethany A. Horsburgh, Bonnie Hiener, Xiao Qian Wang, Timothy E. Schlub, Mark Fitch, Rebecca Hoh, Frederick Hecht, Jeffrey N. Martin, Steven G. Deeks, Marc K. Hellerstein, Joseph M. McCune, Peter W. Hunt, Sarah Palmer
Abstract
The design of future HIV-1 curative therapies requires a more thorough understanding of the distribution of genetically-intact HIV-1 within T-cell subsets as well as the cellular mechanisms that maintain this reservoir. These genetically-intact and presumably replication-competent proviruses make up the latent HIV-1 reservoir. Our investigations into the possible cellular mechanisms maintaining the HIV-1 reservoir in different T-cell subsets have revealed a link between the half-lives of T-cells and the level of proviruses they contain. Taken together, we believe our study shows that more differentiated and proliferative cells, such as transitional and effector memory T-cells, contain the highest levels of genetically-intact proviruses, and the rapid turnover rate of these cells contributes to the expansion of genetically-intact proviruses within them. Therefore, our study delivers an in-depth assessment of the cellular mechanisms, such as cellular proliferation and half-life, that contribute to and maintain the latent HIV-1 reservoir.