Date Published:
2019 04

Publication Type:
Journal Article

Authors:

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

Secondary:
Nat Microbiol

Volume:
4

Pagination:
633-644

Issue:
4

URL:
https://pubmed.ncbi.nlm.nih.gov/

DOI:
10.1038/s41564-018-0335-z

Keywords:
Adult;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

Abstract:
<p>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.</p>