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 HosmalinMorgane Bomsel

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29 Scopus citations

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

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ASJC Scopus subject areas

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

Cite this

Ganor, Y., Real, F., Sennepin, A., Dutertre, C. A., Prevedel, L., Xu, L., Tudor, D., Charmeteau, B., Couedel-Courteille, A., Marion, S., Zenak, A. R., Jourdain, J. P., Zhou, Z., Schmitt, A., Capron, C., Eugenin, E., Cheynier, R., Revol, M., Cristofari, S., ... 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