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

• Published in: Nature microbiology Vol. 4; no. 4; pp. 633 - 644
• Main Authors: 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 A, Cheynier, Rémi, Revol, Marc, Cristofari, Sarra, Hosmalin, Anne, Bomsel, Morgane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/31; 13/51; 14; 14/19; 14/28; 38/77; 38/91; 631/250; 631/250/255; 631/250/255/1901; 631/250/347; Adult; Anti-Retroviral Agents - administration & dosage; Antiretroviral drugs; Antiretroviral therapy; Biomedical and Life Sciences; CD163 antigen; CD4-Positive T-Lymphocytes - virology; Cytokines; Deoxyribonucleic acid; Disease Reservoirs - virology; Disease transmission; DNA; Drug therapy; Female; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; HIV-1 - physiology; Human health and pathology; Human immunodeficiency virus; Humans; Immunology; Infectious Diseases; Interleukin 1; Interleukin 4; Life Sciences; Lipopolysaccharides; Lymphocytes T; Macrophages; Macrophages - virology; Male; Medical Microbiology; Microbiology; Middle Aged; Mucosa; Parasitology; Penis; Reproductive Biology; Ribonucleic acid; RNA; RNA, Viral - genetics; Sexual transmission; Urethra - virology; Virions; Virology; Virus Replication - drug effects
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-018-0335-z

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. Suppressive combination antiretroviral therapy fails to eradicate HIV-1 latent reservoirs in poorly characterized cell compartments. Here, urethral macrophages, but not urethral T cells, are shown to contain integrated HIV-1 DNA and to be able to release infectious HIV-1 following reactivation with lipopolysaccharide.