Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103 <sup>+</sup> and Gut CD4 <sup>+</sup> T Cells
Steven A. Yukl, Shahzada Khan, Tsui‐Hua Chen, Martin Trapečar, Frank Shao-Ying Wu, Guorui Xie, Sushama Telwatte, Daniel Fulop, Alexander R. Pico, Gregory M. Laird, Kristen D. Ritter, Norman G. Jones, Chuanyi M. Lu, Robert F. Siliciano, Nadia R. Roan, Jeffrey M. Milush, Ma Somsouk, Steven G. Deeks, Peter W. Hunt, Shomyseh Sanjabi
Abstract
The ability of HIV to establish a reversibly silent, “latent” infection is widely regarded as the main barrier to curing HIV. Most HIV-infected cells reside in tissues such as the gut, but it is unclear what mechanisms maintain HIV latency in the blood or gut. We found that circulating CD103 + CD4 + T cells are enriched for HIV-infected cells in a latent-like state. Using RNA sequencing (RNA-seq), we found that CD103 + T cells share a cellular transcriptome that more closely resembles that of CD4 + T cells from the gut, suggesting that they are homing to or from the gut. We also identified the cellular genes whose expression distinguishes gut CD4 + or circulating CD103 + T cells from circulating CD103 − T cells, including some genes that have been implicated in HIV expression. These genes may contribute to latent HIV infection in the gut and may serve as new targets for therapies aimed at curing HIV.