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Related Experiment Videos

CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function

R Mariani1, S Wong, L C Mulder

  • 1Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.

Journal of Virology
|February 11, 1999
PubMed
Summary
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The CCR2-64I polymorphism, linked to slower AIDS progression in HIV, does not affect CCR5 coreceptor function or expression levels. This suggests the polymorphism

Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • A CCR2 gene polymorphism (CCR2-64I) is linked to delayed AIDS progression in HIV-infected individuals.
  • The CCR2-64I variant involves an amino acid change from valine to isoleucine.
  • The exact mechanism behind this protective effect is unclear, with possibilities including direct effects of the amino acid change or linkage to other mutations.

Purpose of the Study:

  • To investigate whether the CCR2-64I polymorphism directly impacts CCR5 coreceptor function and expression.
  • To determine if linked CCR5 promoter polymorphisms contribute to the observed association with slowed AIDS pathogenesis.
  • To elucidate the molecular mechanisms underlying the CCR2-64I association with HIV disease progression.

Main Methods:

  • Assessed CCR5 and CCR2 expression on peripheral blood mononuclear cells (PBMC) from donors with different CCR2/CCR5 genotypes.

Related Experiment Videos

  • Utilized flow cytometry to quantify cell surface protein levels.
  • Employed reporter gene assays to evaluate the transcriptional activity of linked CCR5 promoter polymorphisms.

    • Main Results:

    • CCR2-64I polymorphism did not impair CCR5 coreceptor function.
    • Activated CD4(+) T cells from CCR2-64I/64I donors showed comparable CCR5 cell surface expression to CCR2 +/+ donors.
    • CCR5 and CCR2 mRNA levels were similar across genotypes, though cell surface levels showed more variability.
    • Linked CCR5 promoter polymorphisms (208G, 303A, 627C, 676A) did not alter transcriptional activity in reporter assays.

    Conclusions:

    • The CCR2-64I polymorphism does not appear to influence AIDS progression by altering CCR5 transcription or mRNA levels.
    • The protective effect of CCR2-64I is unlikely mediated through direct effects on CCR5 coreceptor function or expression.
    • Further research is needed to identify the precise mechanism linking CCR2-64I to delayed AIDS progression.