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 A. Eugenin, Rémi Cheynier, Marc Revol, Sarra Cristofari, Anne HosmalinMorgane Bomsel

Research output: Contribution to journalArticlepeer-review

62 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)
Pages (from-to)633-644
Number of pages12
JournalNature Microbiology
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2019

ASJC Scopus subject areas

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

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