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

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.
Complete list of metadatas

Cited literature [69 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02019067
Contributor : Morgane Bomsel <>
Submitted on : Thursday, February 14, 2019 - 12:03:47 PM
Last modification on : Friday, August 9, 2019 - 3:24:03 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Yonatan Ganor, Fernando Real, Alexis Sennepin, Charles-Antoine Dutertre, Lisa Prevedel, et al.. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nature Microbiology, Nature Publishing Group, 2019, Epub ahead of print. ⟨10.1038/s41564-018-0335-z⟩. ⟨inserm-02019067⟩

Share

Metrics

Record views

128