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

Yonatan Ganor^{1

2

3}, Fernando Real^#^{4

5

6}, Alexis Sennepin^#^{4

5

6}, Charles-Antoine Dutertre^{5

6

7

8}, Lisa Prevedel^{9

10}, Lin Xu^{4

5

6}, Daniela Tudor^{4

5

6}, Bénédicte Charmeteau^{5

6

11}, Anne Couedel-Courteille^{5

6

11}, Sabrina Marion^{4

5

6}, Ali-Redha Zenak^{4

5

6}, Jean-Pierre Jourdain^{5

6

7}, Zhicheng Zhou^{4

5

6}, Alain Schmitt^{5

6

12}, Claude Capron¹³, Eliseo A Eugenin^{9

10}, Rémi Cheynier^{5

6

11}, Marc Revol¹⁴, Sarra Cristofari¹⁴, Anne Hosmalin^{5

6

7}, Morgane Bomsel^{15

16

17}

Affiliations

¹ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France. yonatan.ganor@inserm.fr.
² INSERM U1016, Paris, France. yonatan.ganor@inserm.fr.
³ Université Paris Descartes, Sorbonne Paris Cité, Paris, France. yonatan.ganor@inserm.fr.
⁴ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
⁵ INSERM U1016, Paris, France.
⁶ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
⁷ Laboratory of Dendritic Cell Immunobiology, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
⁸ Program in Emerging Infectious Disease, Duke-National University of Singapore Medical School, Singapore, Singapore.
⁹ Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA.
¹⁰ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA.
¹¹ Laboratory of Cytokines and Viral Infections, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
¹² Electron Microscopy Platform Laboratory, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
¹³ Hematology and Immunology Service, Ambroise Paré Hospital, Boulogne, France.
¹⁴ Plastic, Reconstructive and Aesthetic Surgery Department, Saint Louis Hospital, Paris, France.
¹⁵ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France. morgane.bomsel@inserm.fr.
¹⁶ INSERM U1016, Paris, France. morgane.bomsel@inserm.fr.
¹⁷ Université Paris Descartes, Sorbonne Paris Cité, Paris, France. morgane.bomsel@inserm.fr.

^# Contributed equally.

PMID: 30718846
DOI: 10.1038/s41564-018-0335-z

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

Yonatan Ganor et al. Nat Microbiol. 2019 Apr.

. 2019 Apr;4(4):633-644.

doi: 10.1038/s41564-018-0335-z. Epub 2019 Feb 4.

Authors

Affiliations

¹ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France. yonatan.ganor@inserm.fr.
² INSERM U1016, Paris, France. yonatan.ganor@inserm.fr.
³ Université Paris Descartes, Sorbonne Paris Cité, Paris, France. yonatan.ganor@inserm.fr.
⁴ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
⁵ INSERM U1016, Paris, France.
⁶ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
⁷ Laboratory of Dendritic Cell Immunobiology, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
⁸ Program in Emerging Infectious Disease, Duke-National University of Singapore Medical School, Singapore, Singapore.
⁹ Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA.
¹⁰ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA.
¹¹ Laboratory of Cytokines and Viral Infections, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
¹² Electron Microscopy Platform Laboratory, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France.
¹³ Hematology and Immunology Service, Ambroise Paré Hospital, Boulogne, France.
¹⁴ Plastic, Reconstructive and Aesthetic Surgery Department, Saint Louis Hospital, Paris, France.
¹⁵ Laboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity and Inflammation, Cochin Institute, CNRS UMR8104, Paris, France. morgane.bomsel@inserm.fr.
¹⁶ INSERM U1016, Paris, France. morgane.bomsel@inserm.fr.
¹⁷ Université Paris Descartes, Sorbonne Paris Cité, Paris, France. morgane.bomsel@inserm.fr.

^# Contributed equally.

PMID: 30718846
DOI: 10.1038/s41564-018-0335-z

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.

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Comment in

Urethral macrophages - a new HIV-1 reservoir.
Bradley CA. Bradley CA. Nat Rev Urol. 2019 Apr;16(4):205. doi: 10.1038/s41585-019-0158-6. Nat Rev Urol. 2019. PMID: 30742046 No abstract available.
Macrophages hide HIV in the urethra.
Rodrigues V, Benaroch P. Rodrigues V, et al. Nat Microbiol. 2019 Apr;4(4):556-557. doi: 10.1038/s41564-019-0418-5. Nat Microbiol. 2019. PMID: 30899108 No abstract available.

References

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1. Clayton, K. L. et al. Resistance of HIV-infected macrophages to CD8⁺ T lymphocyte-mediated killing drives activation of the immune system. Nat. Immunol. 19, 475–486 (2018). - DOI

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

Affiliations

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

Authors

Affiliations

Abstract

Comment in

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials