HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy

Yonatan Ganor, Fernando Real, Alexis Sennepin, Charles Antoine Dutertre, Lisa Prevedel, Lin Xu, Daniela Tudor, Bénédicte Charmeteau, Anne Couedel-Courteille, Sabrina Marion, Ali Redha Zenak, Jean Pierre Jourdain, Zhicheng Zhou, Alain Schmitt, Claude Capron, Eliseo Eugenin, Rémi Cheynier, Marc Revol, Sarra Cristofari, Anne Hosmalin & 1 others Morgane Bomsel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.

Original languageEnglish (US)
JournalNature Microbiology
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

HIV-1
Macrophages
Therapeutics
Interleukin-4 Receptors
T-Lymphocytes
Virus Internalization
Viral Structures
Interleukin-1 Receptors
Phytohemagglutinins
Virion
Lipopolysaccharides
Mucous Membrane
RNA
Viruses
DNA
Infection
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. / Ganor, Yonatan; Real, Fernando; Sennepin, Alexis; Dutertre, Charles Antoine; Prevedel, Lisa; Xu, Lin; Tudor, Daniela; Charmeteau, Bénédicte; Couedel-Courteille, Anne; Marion, Sabrina; Zenak, Ali Redha; Jourdain, Jean Pierre; Zhou, Zhicheng; Schmitt, Alain; Capron, Claude; Eugenin, Eliseo; Cheynier, Rémi; Revol, Marc; Cristofari, Sarra; Hosmalin, Anne; Bomsel, Morgane.

In: Nature Microbiology, 01.01.2019.

Research output: Contribution to journalArticle

Ganor, Y, Real, F, Sennepin, A, Dutertre, CA, Prevedel, L, Xu, L, Tudor, D, Charmeteau, B, Couedel-Courteille, A, Marion, S, Zenak, AR, Jourdain, JP, Zhou, Z, Schmitt, A, Capron, C, Eugenin, E, Cheynier, R, Revol, M, Cristofari, S, Hosmalin, A & Bomsel, M 2019, 'HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy', Nature Microbiology. https://doi.org/10.1038/s41564-018-0335-z
Ganor, Yonatan ; Real, Fernando ; Sennepin, Alexis ; Dutertre, Charles Antoine ; Prevedel, Lisa ; Xu, Lin ; Tudor, Daniela ; Charmeteau, Bénédicte ; Couedel-Courteille, Anne ; Marion, Sabrina ; Zenak, Ali Redha ; Jourdain, Jean Pierre ; Zhou, Zhicheng ; Schmitt, Alain ; Capron, Claude ; Eugenin, Eliseo ; Cheynier, Rémi ; Revol, Marc ; Cristofari, Sarra ; Hosmalin, Anne ; Bomsel, Morgane. / HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. In: Nature Microbiology. 2019.
@article{44b028fb1d5d49ad99c9965a68283b01,
title = "HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy",
abstract = "Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.",
author = "Yonatan Ganor and Fernando Real and Alexis Sennepin and Dutertre, {Charles Antoine} and Lisa Prevedel and Lin Xu and Daniela Tudor and B{\'e}n{\'e}dicte Charmeteau and Anne Couedel-Courteille and Sabrina Marion and Zenak, {Ali Redha} and Jourdain, {Jean Pierre} and Zhicheng Zhou and Alain Schmitt and Claude Capron and Eliseo Eugenin and R{\'e}mi Cheynier and Marc Revol and Sarra Cristofari and Anne Hosmalin and Morgane Bomsel",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41564-018-0335-z",
language = "English (US)",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy

AU - Ganor, Yonatan

AU - Real, Fernando

AU - Sennepin, Alexis

AU - Dutertre, Charles Antoine

AU - Prevedel, Lisa

AU - Xu, Lin

AU - Tudor, Daniela

AU - Charmeteau, Bénédicte

AU - Couedel-Courteille, Anne

AU - Marion, Sabrina

AU - Zenak, Ali Redha

AU - Jourdain, Jean Pierre

AU - Zhou, Zhicheng

AU - Schmitt, Alain

AU - Capron, Claude

AU - Eugenin, Eliseo

AU - Cheynier, Rémi

AU - Revol, Marc

AU - Cristofari, Sarra

AU - Hosmalin, Anne

AU - Bomsel, Morgane

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.

AB - Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.

UR - http://www.scopus.com/inward/record.url?scp=85061035996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061035996&partnerID=8YFLogxK

U2 - 10.1038/s41564-018-0335-z

DO - 10.1038/s41564-018-0335-z

M3 - Article

JO - Nature Microbiology

JF - Nature Microbiology

SN - 2058-5276

ER -