TGF-β Signaling Supports HIV Latency in a Memory CD4+ T Cell Based In Vitro Model

During antiretroviral therapy (ART), HIV-1 persists as a latent reservoir in CD4+ T cell subsets in central (T_CM), transitional (T_TM) and effector memory (T_EM) CD4+ T cells. Understanding the mechanisms that support HIV-1 latency in each of these subsets is essential to the identification of cure strategies to eliminate them. Due to the very low frequency of latently infected cells in vivo, model systems that can accurately reflect the heterogenous population of HIV-1 infected cells are a critical component in HIV cure discoveries. Here, we describe a novel primary cell-based model of HIV-1 latency that recapitulates the complex dynamics of the establishment and maintenance of the latent reservoir in different memory T cell subsets. The latency and reversion assay (LARA ) culture conditions uniquely retain phenotypically and transcriptionally distinct memory CD4+ T cell subsets that allow in a single assay to assess LRA activity in each memory subset and differential examination of the dynamics of HIV latency reversal.