HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells.

HIV-1 replicates in CD4 ⁺ T cells, leading to AIDS. Determining how HIV-1 shapes its niche to create a permissive environment is central to informing efforts to limit pathogenesis, disturb reservoirs, and achieve a cure. A key roadblock in understanding HIV-T cell interactions is the requirement to activate T cells in vitro to make them permissive to infection. This dramatically alters T cell biology and virus-host interactions. Here we show that HIV-1 cell-to-cell spread permits efficient, productive infection of resting memory T cells without prior activation. Strikingly, we find that HIV-1 infection primes resting T cells to gain characteristics of tissue-resident memory T cells (T _RM ), including upregulating key surface markers and the transcription factor Blimp-1 and inducing a transcriptional program overlapping the core T _RM transcriptional signature. This reprogramming is driven by Vpr and requires Vpr packaging into virions and manipulation of STAT5. Thus, HIV-1 reprograms resting T cells, with implications for viral replication and persistence.
Competing Interests: Declaration of interests L.J.P. participates in advisory boards and provides consultancy to SQZ Biotech.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)