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Article Dans Une Revue Nature Microbiology Année : 2019

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

Yonatan Ganor
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Lin Xu
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Daniela Tudor
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Rémi Cheynier
Morgane Bomsel
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Résumé

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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Dates et versions

inserm-02019067 , version 1 (14-02-2019)

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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, 2019, 4, pp.633-644. ⟨10.1038/s41564-018-0335-z⟩. ⟨inserm-02019067⟩
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