Transcriptional response of HIV-infected CD4 memory T cells to co-culture with TCR activated CD8 T cells.

The persistence of HIV infection under ART is due to a reservoir of latently infected cells that harbor replication-competent virus and evade immune recognition. Defining the mechanisms responsible for the establishment and maintenance of HIV latency is crucial to achieve HIV eradication or functional cure. Previous studies demonstrated a non-cytotoxic CD8+ T-cells mediated inhibition of virus replication during untreated HIV/SIV infection and inhibition of virus production under ART; however, the mechanisms responsible for this antiviral effect remained poorly understood. In our primary cell-based in vitro latency model we demonstrated that co-culture with CD8+ T-cells promotes changes in metabolic and cell survival pathways in HIV-infected memory CD4+ T-cells that may negatively regulate HIV expression and ultimately promote the establishment of latency. Modulation of this CD8-mediated activity may represent a tool to disrupt HIV latency and reservoir persistence in ART-treated individuals. Peripheral blood mononuclear cells (PBMC) were isolated from HIV naïve healthy donors. From each donor memory CD4+ T cells were enriched and infected with HIV, and CD8+ T cells were selected and TCR-activated. RNA was extracted from HIV infected memory CD4+ T cells were that were mono-cultured and co-cultured with TCR-activated CD8+ T cells.