HIV-1 vpr induces widespread transcriptomic changes in CD4+ T cells early postinfection

Hélène Bauby; Christopher C. Ward; Rupert Hugh-White; Chad M. Swanson; Reiner Schulz; Caroline Goujon; Michael H. Malima

doi:10.1128/mBio.01369-21

HIV-1 vpr induces widespread transcriptomic changes in CD4+ T cells early postinfection

Hélène Bauby, Christopher C. Ward, Rupert Hugh-White, Chad M. Swanson, Reiner Schulz, Caroline Goujon^*, Michael H. Malima

^*Corresponding author for this work

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

12 Citations (Scopus)

Abstract

The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD41 T cells during the first 24 h of infection. Here, we analyzed CD41 T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD41 T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic development. Previous studies have used transcriptomics to assess gene expression changes in CD41 T cells following HIV-1 infection; here, we provide a detailed examination of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This finding has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.

Original language	English
Article number	e01369-21
Journal	Mbio
Volume	12
Issue number	3
DOIs	https://doi.org/10.1128/mBio.01369-21
Publication status	Published - Jun 2021

Keywords

HIV
Transcriptomics
Virus-host interactions
Vpr

UN SDGs

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

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10.1128/mBio.01369-21

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title = "HIV-1 vpr induces widespread transcriptomic changes in CD4+ T cells early postinfection",

abstract = "The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD41 T cells during the first 24 h of infection. Here, we analyzed CD41 T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD41 T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic development. Previous studies have used transcriptomics to assess gene expression changes in CD41 T cells following HIV-1 infection; here, we provide a detailed examination of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This finding has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.",

keywords = "HIV, Transcriptomics, Virus-host interactions, Vpr",

author = "H{\'e}l{\`e}ne Bauby and Ward, {Christopher C.} and Rupert Hugh-White and Swanson, {Chad M.} and Reiner Schulz and Caroline Goujon and Malima, {Michael H.}",

note = "Funding Information: This work was supported by the UK Medical Research Council (grants G0401570 and G1000196 to M.H.M.), The Wellcome Trust (grant 106223/Z/14/Z to M.H.M.), the National Institutes of Health (grant DA033773), the European Commission?s Seventh Framework Program (grant FP7/2007-2013) under grant agreement no. PIEF-GA-2009- 237501 (to C.G.), a Wellcome Trust Research Training Fellowship (grant 103407/Z/13/Z to C.C.W.), an NIHR Academic Clinical Lectureship grant (to C.C.W.), a Guy?s and St. Thomas? Charity Prize Ph.D. Program in Biomedical and Translational Science studentship (to R.H.-W.), and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy?s and St. Thomas? NHS Foundation Trust in partnership with King?s College London and the King?s College Hospital NHS Foundation Trust. Funding Information: This work was supported by the UK Medical Research Council (grants G0401570 and G1000196 to M.H.M.), The Wellcome Trust (grant 106223/Z/14/Z to M.H.M.), the National Institutes of Health (grant DA033773), the European Commission{\textquoteright}s Seventh Framework Program (grant FP7/2007-2013) under grant agreement no. PIEF-GA-2009-237501 (to C.G.), a Wellcome Trust Research Training Fellowship (grant 103407/Z/13/Z to C.C.W.), an NIHR Academic Clinical Lectureship grant (to C.C.W.), a Guy{\textquoteright}s and St. Thomas{\textquoteright} Charity Prize Ph.D. Program in Biomedical and Translational Science studentship (to R.H.-W.), and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy{\textquoteright}s and St. Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London and the King{\textquoteright}s College Hospital NHS Foundation Trust. Publisher Copyright: {\textcopyright} 2021 Bauby et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jun,

doi = "10.1128/mBio.01369-21",

language = "English",

volume = "12",

journal = "Mbio",

issn = "2161-2129",

publisher = "American Society for Microbiology",

number = "3",

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TY - JOUR

T1 - HIV-1 vpr induces widespread transcriptomic changes in CD4+ T cells early postinfection

AU - Bauby, Hélène

AU - Ward, Christopher C.

AU - Hugh-White, Rupert

AU - Swanson, Chad M.

AU - Schulz, Reiner

AU - Goujon, Caroline

AU - Malima, Michael H.

N1 - Funding Information: This work was supported by the UK Medical Research Council (grants G0401570 and G1000196 to M.H.M.), The Wellcome Trust (grant 106223/Z/14/Z to M.H.M.), the National Institutes of Health (grant DA033773), the European Commission?s Seventh Framework Program (grant FP7/2007-2013) under grant agreement no. PIEF-GA-2009- 237501 (to C.G.), a Wellcome Trust Research Training Fellowship (grant 103407/Z/13/Z to C.C.W.), an NIHR Academic Clinical Lectureship grant (to C.C.W.), a Guy?s and St. Thomas? Charity Prize Ph.D. Program in Biomedical and Translational Science studentship (to R.H.-W.), and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy?s and St. Thomas? NHS Foundation Trust in partnership with King?s College London and the King?s College Hospital NHS Foundation Trust. Funding Information: This work was supported by the UK Medical Research Council (grants G0401570 and G1000196 to M.H.M.), The Wellcome Trust (grant 106223/Z/14/Z to M.H.M.), the National Institutes of Health (grant DA033773), the European Commission’s Seventh Framework Program (grant FP7/2007-2013) under grant agreement no. PIEF-GA-2009-237501 (to C.G.), a Wellcome Trust Research Training Fellowship (grant 103407/Z/13/Z to C.C.W.), an NIHR Academic Clinical Lectureship grant (to C.C.W.), a Guy’s and St. Thomas’ Charity Prize Ph.D. Program in Biomedical and Translational Science studentship (to R.H.-W.), and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London and the King’s College Hospital NHS Foundation Trust. Publisher Copyright: © 2021 Bauby et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD41 T cells during the first 24 h of infection. Here, we analyzed CD41 T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD41 T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic development. Previous studies have used transcriptomics to assess gene expression changes in CD41 T cells following HIV-1 infection; here, we provide a detailed examination of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This finding has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.

AB - The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD41 T cells during the first 24 h of infection. Here, we analyzed CD41 T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD41 T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic development. Previous studies have used transcriptomics to assess gene expression changes in CD41 T cells following HIV-1 infection; here, we provide a detailed examination of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This finding has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.

KW - HIV

KW - Transcriptomics

KW - Virus-host interactions

KW - Vpr

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U2 - 10.1128/mBio.01369-21

DO - 10.1128/mBio.01369-21

M3 - Article

C2 - 34154423

AN - SCOPUS:85110228829

SN - 2161-2129

VL - 12

JO - Mbio

JF - Mbio

IS - 3

M1 - e01369-21

ER -

HIV-1 vpr induces widespread transcriptomic changes in CD4+ T cells early postinfection

Abstract

Keywords

UN SDGs

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