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

doi:10.1038/s41564-018-0335-z

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

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

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.

PubMed Disclaimer

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.

Cited by

Lnc(ing)RNAs to the "shock and kill" strategy for HIV-1 cure.
Boliar S, Russell DG. Boliar S, et al. Mol Ther Nucleic Acids. 2021 Feb 10;23:1272-1280. doi: 10.1016/j.omtn.2021.02.004. eCollection 2021 Mar 5. Mol Ther Nucleic Acids. 2021. PMID: 33717648 Free PMC article. Review.
Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP.
Cui J, Meshesha M, Churgulia N, Merlo C, Fuchs E, Breakey J, Jones J, Stivers JT. Cui J, et al. Retrovirology. 2022 Sep 16;19(1):21. doi: 10.1186/s12977-022-00607-2. Retrovirology. 2022. PMID: 36114511 Free PMC article.
TREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial Function.
Campbell GR, To RK, Spector SA. Campbell GR, et al. mBio. 2019 Nov 12;10(6):e02638-19. doi: 10.1128/mBio.02638-19. mBio. 2019. PMID: 31719184 Free PMC article.
HIV Latency in Myeloid Cells: Challenges for a Cure.
Chitrakar A, Sanz M, Maggirwar SB, Soriano-Sarabia N. Chitrakar A, et al. Pathogens. 2022 May 24;11(6):611. doi: 10.3390/pathogens11060611. Pathogens. 2022. PMID: 35745465 Free PMC article. Review.
HIV-1-induced type I IFNs promote viral latency in macrophages.
Dickey LL, Martins LJ, Planelles V, Hanley TM. Dickey LL, et al. J Leukoc Biol. 2022 Nov;112(5):1343-1356. doi: 10.1002/JLB.4MA0422-616R. Epub 2022 May 19. J Leukoc Biol. 2022. PMID: 35588262 Free PMC article.

See all "Cited by" articles

References

1. Sengupta, S. & Siliciano, R. F. Targeting the latent reservoir for HIV-1. Immunity 48, 872–895 (2018). - DOI
1. Gaudin, R. et al. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections. PLoS ONE 8, e69450 (2013). - DOI
1. Castellano, P., Prevedel, L. & Eugenin, E. A. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci. Rep. 7, 12866 (2017). - DOI
1. Swingler, S., Mann, A. M., Zhou, J., Swingler, C. & Stevenson, M. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog. 3, 1281–1290 (2007). - DOI
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

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Sengupta, S. & Siliciano, R. F. Targeting the latent reservoir for HIV-1. Immunity 48, 872–895 (2018). - DOI

[2] Sengupta, S. & Siliciano, R. F. Targeting the latent reservoir for HIV-1. Immunity 48, 872–895 (2018). - DOI

[3] Gaudin, R. et al. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections. PLoS ONE 8, e69450 (2013). - DOI

[4] Gaudin, R. et al. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections. PLoS ONE 8, e69450 (2013). - DOI

[5] Castellano, P., Prevedel, L. & Eugenin, E. A. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci. Rep. 7, 12866 (2017). - DOI

[6] Castellano, P., Prevedel, L. & Eugenin, E. A. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci. Rep. 7, 12866 (2017). - DOI

[7] Swingler, S., Mann, A. M., Zhou, J., Swingler, C. & Stevenson, M. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog. 3, 1281–1290 (2007). - DOI

[8] Swingler, S., Mann, A. M., Zhou, J., Swingler, C. & Stevenson, M. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog. 3, 1281–1290 (2007). - DOI

[9] 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

[10] 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

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Abstract

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Research Materials