TY - JOUR
T1 - HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy
AU - Ganor, Yonatan
AU - Real, Fernando
AU - Sennepin, Alexis
AU - Dutertre, Charles Antoine
AU - Prevedel, Lisa
AU - Xu, Lin
AU - Tudor, Daniela
AU - Charmeteau, Bénédicte
AU - Couedel-Courteille, Anne
AU - Marion, Sabrina
AU - Zenak, Ali Redha
AU - Jourdain, Jean Pierre
AU - Zhou, Zhicheng
AU - Schmitt, Alain
AU - Capron, Claude
AU - Eugenin, Eliseo A.
AU - Cheynier, Rémi
AU - Revol, Marc
AU - Cristofari, Sarra
AU - Hosmalin, Anne
AU - Bomsel, Morgane
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41564-018-0335-z
DO - 10.1038/s41564-018-0335-z
M3 - Article
C2 - 30718846
AN - SCOPUS:85061035996
SN - 2058-5276
VL - 4
SP - 633
EP - 644
JO - Nature Microbiology
JF - Nature Microbiology
IS - 4
ER -