Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.
Mathieu A F ClaireauxRemy RobinotJérôme KervevanMandar PatgaonkarIsabelle StaropoliAnne BrelotAlexandre NouëlStacy GellenoncourtXian TangMélanie HéryStevenn VolantEmeline PerthameVeronique Avettand-FenoelJulian BuchrieserThomas CokelaerChristiane BouchierLaurence MaFaroudy BoufassaSamia HendouValentina LibriMilena HasanDavid ZucmanPierre de TruchisOlivier SchwartzOlivier LambotteLisa A ChakrabartiPublished in: Nature communications (2022)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- regulatory t cells
- dendritic cells
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- poor prognosis
- induced apoptosis
- end stage renal disease
- chronic kidney disease
- cell proliferation
- sars cov
- ejection fraction
- cell cycle arrest
- copy number
- peritoneal dialysis
- prognostic factors
- autism spectrum disorder
- intellectual disability
- patient reported