Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.

Autor: Claireaux M; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Robinot R; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Kervevan J; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Patgaonkar M; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Staropoli I; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Brelot A; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Nouël A; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Gellenoncourt S; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Tang X; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Héry M; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Volant S; Bioinformatics and Biostatistics Hub, Department of Computational Biology, Institut Pasteur, Université de Paris, Paris, France., Perthame E; Bioinformatics and Biostatistics Hub, Department of Computational Biology, Institut Pasteur, Université de Paris, Paris, France., Avettand-Fenoël V; AP-HP Hôpital Necker-Enfants Malades, Laboratoire de Microbiologie clinique, Paris, France.; CNRS 8104, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France., Buchrieser J; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Cokelaer T; Bioinformatics and Biostatistics Hub, Department of Computational Biology, Institut Pasteur, Université de Paris, Paris, France.; Biomics Platform, C2RT, Institut Pasteur, Université de Paris, Paris, France., Bouchier C; Biomics Platform, C2RT, Institut Pasteur, Université de Paris, Paris, France., Ma L; Biomics Platform, C2RT, Institut Pasteur, Université de Paris, Paris, France., Boufassa F; INSERM U1018, Center for Research in Epidemiology and Population Health (CESP), Le Kremlin-Bicêtre, France., Hendou S; INSERM U1018, Center for Research in Epidemiology and Population Health (CESP), Le Kremlin-Bicêtre, France., Libri V; Cytometry and Biomarkers (CB UTechS), Translational Research Center, Institut Pasteur, Université de Paris, Paris, France., Hasan M; Cytometry and Biomarkers (CB UTechS), Translational Research Center, Institut Pasteur, Université de Paris, Paris, France., Zucman D; HIV Unit, Foch Hospital, Suresnes, France., de Truchis P; AP-HP, Infectious and Tropical Diseases Department, Raymond Poincaré Hospital, Garches, France., Schwartz O; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France.; CNRS UMR3569, Paris, France., Lambotte O; INSERM U1184, Université Paris Sud, CEA, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.; AP-HP, Department of Internal Medicine and Clinical Immunology, University Hospital Paris Sud, Le Kremlin-Bicêtre, France., Chakrabarti LA; Virus and Immunity Unit, Institut Pasteur, Université de Paris, Paris, France. chakra@pasteur.fr.; CNRS UMR3569, Paris, France. chakra@pasteur.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jan 26; Vol. 13 (1), pp. 521. Date of Electronic Publication: 2022 Jan 26.
DOI: 10.1038/s41467-022-28130-0
Abstrakt: HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.
(© 2022. The Author(s).)
Databáze: MEDLINE
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