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

TitleHIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2019
AuthorsGanor, 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, EA, Cheynier, R, Revol, M, Cristofari, S, Hosmalin, A, Bomsel, M
JournalNat Microbiol
Date Published2019 04
KeywordsAdult, Anti-Retroviral Agents, CD4-Positive T-Lymphocytes, Disease Reservoirs, External, Female, HIV Infections, HIV-1, Humans, Macrophages, Male, Middle Aged, RNA, Viral, Urethra, Virus Replication

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.

Alternate JournalNat Microbiol
PubMed ID30718846