1. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.
- Author
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Claireaux M, Robinot R, Kervevan J, Patgaonkar M, Staropoli I, Brelot A, Nouël A, Gellenoncourt S, Tang X, Héry M, Volant S, Perthame E, Avettand-Fenoël V, Buchrieser J, Cokelaer T, Bouchier C, Ma L, Boufassa F, Hendou S, Libri V, Hasan M, Zucman D, de Truchis P, Schwartz O, Lambotte O, and Chakrabarti LA
- Subjects
- Chemokines, Down-Regulation, Gene Expression Regulation, Gene Products, gag metabolism, HIV Infections virology, Histocompatibility Antigens Class II, Humans, Mutation, Receptors, CCR5 genetics, Receptors, CXCR3, CD4-Positive T-Lymphocytes immunology, Elite Controllers, HIV Infections immunology, HIV-1 immunology, Receptors, CCR5 metabolism, Virus Internalization
- 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., (© 2022. The Author(s).)
- Published
- 2022
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