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

Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre Truchis, Olivier Schwartz, Olivier Lambotte and Lisa A. Chakrabarti ()
Additional contact information
Mathieu Claireaux: Université de Paris
Rémy Robinot: Université de Paris
Jérôme Kervevan: Université de Paris
Mandar Patgaonkar: Université de Paris
Isabelle Staropoli: Université de Paris
Anne Brelot: Université de Paris
Alexandre Nouël: Université de Paris
Stacy Gellenoncourt: Université de Paris
Xian Tang: Université de Paris
Mélanie Héry: Université de Paris
Stevenn Volant: Université de Paris
Emeline Perthame: Université de Paris
Véronique Avettand-Fenoël: Laboratoire de Microbiologie clinique
Julian Buchrieser: Université de Paris
Thomas Cokelaer: Université de Paris
Christiane Bouchier: Université de Paris
Laurence Ma: Université de Paris
Faroudy Boufassa: INSERM U1018, Center for Research in Epidemiology and Population Health (CESP)
Samia Hendou: INSERM U1018, Center for Research in Epidemiology and Population Health (CESP)
Valentina Libri: Université de Paris
Milena Hasan: Université de Paris
David Zucman: HIV Unit, Foch Hospital
Pierre Truchis: Raymond Poincaré Hospital
Olivier Schwartz: Université de Paris
Olivier Lambotte: INSERM U1184, Université Paris Sud, CEA, Center for Immunology of Viral Infections and Autoimmune Diseases
Lisa A. Chakrabarti: Université de Paris

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28130-0

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DOI: 10.1038/s41467-022-28130-0

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