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

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03654265
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Submitted on : Thursday, April 28, 2022 - 2:47:56 PM
Last modification on : Friday, August 5, 2022 - 12:03:07 PM
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Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, et al.. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry. Nature Communications, Nature Publishing Group, 2022, 13 (1), pp.521. ⟨10.1038/s41467-022-28130-0⟩. ⟨pasteur-03654265⟩

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