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

Autor: Reuschl AK; Division of Infection and Immunity, University College London, London WC1E 6BT, UK. Electronic address: a.reuschl@ucl.ac.uk., Mesner D; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Shivkumar M; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Whelan MVX; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Pallett LJ; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Guerra-Assunção JA; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Madansein R; Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban 4091, South Africa; Centre for the AIDS Programme of Research in South Africa, Durban 4091, South Africa., Dullabh KJ; Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban 4091, South Africa., Sigal A; Africa Health Research Institute, Durban 4001, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4091, South Africa; Max Planck Institute for Infection Biology, 10117 Berlin, Germany., Thornhill JP; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3XY, UK; Department of Infectious Disease, Faculty of Medicine, Imperial College, London W2 1NY, UK., Herrera C; Department of Infectious Disease, Faculty of Medicine, Imperial College, London W2 1NY, UK., Fidler S; Department of Infectious Disease, Faculty of Medicine, Imperial College, London W2 1NY, UK; Imperial College NIHR Biomedical Research Centre, London W2 1NY, UK., Noursadeghi M; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Maini MK; Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Jolly C; Division of Infection and Immunity, University College London, London WC1E 6BT, UK. Electronic address: c.jolly@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2022 Apr 12; Vol. 39 (2), pp. 110650.
DOI: 10.1016/j.celrep.2022.110650
Abstrakt: 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.)
Databáze: MEDLINE
Externí odkaz: