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

Ann Kathrin Reuschl; Dejan Mesner; Maitreyi Shivkumar; Matthew V.X. Whelan; Laura J. Pallett; José Afonso Guerra-Assunção; Rajhmun Madansein; Kaylesh J. Dullabh; Alex Sigal; John P. Thornhill; Carolina Herrera; Sarah Fidler; Mahdad Noursadeghi; Mala K. Maini; Clare Jolly

doi:10.1016/j.celrep.2022.110650

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

Ann Kathrin Reuschl^*
, Dejan Mesner
, Maitreyi Shivkumar
, Matthew V.X. Whelan
, Laura J. Pallett
, José Afonso Guerra-Assunção
, Rajhmun Madansein
, Kaylesh J. Dullabh
, Alex Sigal
, John P. Thornhill
, Carolina Herrera
, Sarah Fidler
, Mahdad Noursadeghi
, Mala K. Maini
, Clare Jolly^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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 (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.

Original language	English
Article number	110650
Journal	Cell Reports
Volume	39
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2022.110650
State	Published - 12 Apr 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

CP: Immunology
CP: Microbiology
HIV-1
Vpr
cell-cell
permissivity
resting memory T cell
tissue residency
transcriptional reprogramming

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2022.110650

Cite this

Reuschl, A. K., Mesner, D., Shivkumar, M., Whelan, M. V. X., Pallett, L. J., Guerra-Assunção, J. A., Madansein, R., Dullabh, K. J., Sigal, A., Thornhill, J. P., Herrera, C., Fidler, S., Noursadeghi, M., Maini, M. K., & Jolly, C. (2022). HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells. Cell Reports, 39(2), Article 110650. https://doi.org/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.",

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Reuschl, AK, Mesner, D, Shivkumar, M, Whelan, MVX, Pallett, LJ, Guerra-Assunção, JA, Madansein, R, Dullabh, KJ, Sigal, A, Thornhill, JP, Herrera, C, Fidler, S, Noursadeghi, M, Maini, MK & Jolly, C 2022, 'HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells', Cell Reports, vol. 39, no. 2, 110650. https://doi.org/10.1016/j.celrep.2022.110650

TY - JOUR

T1 - HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells

AU - Reuschl, Ann Kathrin

AU - Mesner, Dejan

AU - Shivkumar, Maitreyi

AU - Whelan, Matthew V.X.

AU - Pallett, Laura J.

AU - Guerra-Assunção, José Afonso

AU - Madansein, Rajhmun

AU - Dullabh, Kaylesh J.

AU - Sigal, Alex

AU - Thornhill, John P.

AU - Herrera, Carolina

AU - Fidler, Sarah

AU - Noursadeghi, Mahdad

AU - Maini, Mala K.

AU - Jolly, Clare

PY - 2022/4/12

Y1 - 2022/4/12

N2 - 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.

AB - 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.

KW - CP: Immunology

KW - CP: Microbiology

KW - HIV-1

KW - Vpr

KW - cell-cell

KW - permissivity

KW - resting memory T cell

KW - tissue residency

KW - transcriptional reprogramming

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C2 - 35417711

AN - SCOPUS:85128127479

SN - 2211-1247

VL - 39

JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 110650

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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