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.
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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 |
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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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