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Reduced CCR5 expression among Uganda HIV controllers.

Brian Nyiro1,2, Sharon Bright Amanya3,2, Alice Bayiyana2

  • 1New Jersey Medical School, Rutgers University, New Jersey, USA.

Retrovirology
|May 25, 2023
PubMed
Summary
This summary is machine-generated.

Reduced CCR5 expression on CD4+ T cells is key for HIV control in Ugandan controllers. This mechanism helps maintain high CD4+ T cell counts in individuals not on antiretroviral therapy.

Keywords:
CCR5 promoter polymorphismsElite controllersHIVNon-controllersViremic controllers

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Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • HIV controllers spontaneously control viral load without antiretroviral therapy (ART).
  • Mechanisms of HIV control are diverse and not fully understood, varying among individuals.
  • Reduced CCR5 expression is one proposed mechanism for HIV control.

Purpose of the Study:

  • To investigate the role of reduced CCR5 expression in HIV control among Ugandan HIV controllers.
  • To compare CCR5 expression on CD4+ T cells between HIV controllers and treated non-controllers.

Main Methods:

  • Ex-vivo characterization of CD4+ T cells from archived peripheral blood mononuclear cells (PBMCs).
  • Comparison of CCR5 expression levels between HIV controllers and treated HIV non-controllers.
  • Genotyping for specific CCR5-associated single nucleotide polymorphisms (SNPs).

Main Results:

  • HIV controllers exhibited significantly reduced CCR5 expression on their CD4+ T cells compared to treated non-controllers.
  • The percentage of CCR5+ CD4+ T cells was similar between groups, indicating reduced expression per cell.
  • A subset of controllers carried the rs1799987 SNP (associated with reduced CCR5), while non-controllers had the rs41469351 SNP (associated with increased HIV transmission and mortality).

Conclusions:

  • Reduced CCR5 density on CD4+ T cells plays a crucial role in HIV control among Ugandan controllers.
  • This mechanism contributes to maintaining high CD4+ T cell counts in ART-naïve HIV controllers.