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

Reuschl, Ann-Kathrin; Mesner, Dejan; Shivkumar, Maitreyi; Whelan, Matthew VX; Pallett, Laura J; Guerra-Assunção, José Afonso; Madansein, Rajhmun; ... Jolly, Clare; + view all (2022) HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells. Cell Reports , 39 (2) , Article 110650. 10.1016/j.celrep.2022.110650. Green open access

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Abstract

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 (TRM), including upregulating key surface markers and the transcription factor Blimp-1 and inducing a transcriptional program overlapping the core TRM 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.

Type: Article
Title: HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2022.110650
Publisher version: https://doi.org/10.1016/j.celrep.2022.110650
Language: English
Additional information: Copyright © 2022 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: HIV-1, Vpr, resting memory T cell, cell-cell, tissue residency, permissivity, transcriptional reprogramming
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10147009
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