| HIV infection of primary human T cells requires T cell activation signals. The research detailed herein is aimed to delineate the specific activation and host factor requirements to establish a productive HIV infection within primary T cells. Our results demonstrate that the same threshold and duration of antigen signals that lead to optimal T cell activation are required for productive HIV infection. Utilizing signaling inhibitors and VacA, a toxin produced by Helicobacter pylori, to block activation-induced signaling in primary human CD4+ T cells, we elucidate signaling requirements for HIV infection. Furthermore, we demonstrate that human Treg cells, a T cell subset shown to suppress T cell activation, are highly susceptible to HIV infection and replication. Finally, we identify a subset of human CD4+ effector memory T cells that are expanded during HIV infection and are preferentially susceptible to X4-tropic viral strains. Our results lend novel insight into how HIV exploits T cell signaling mechanisms and host factors that regulate viral replication. Importantly, this work has implications in understanding the role of Treg cells and the chronic activated state of T cells during HIV infection, as well as ascertaining why R5-tropic strains switch to X4-tropic viruses at late stages of HIV infection. |
