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HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism

L Zhang1, C D Carruthers, T He

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

AIDS Research and Human Retroviruses
|November 14, 1997
PubMed
Summary
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Human immunodeficiency virus type 1 (HIV-1) entry relies on CCR5 and CXCR4 coreceptors across diverse subtypes. Viral phenotype, not genotype, dictates coreceptor use, and CCR5 diversity doesn't explain global subtype spread.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • CCR5 and CXCR4 are key coreceptors for HIV-1 entry, crucial for understanding pathogenesis and tropism.
  • Current knowledge primarily stems from studies on HIV-1 subtype B, prevalent in Western regions.
  • Limited understanding exists regarding coreceptor usage across diverse global HIV-1 subtypes.

Purpose of the Study:

  • To investigate the coreceptor usage of HIV-1 isolates from various genetic subtypes (A, B, C, D, E, O).
  • To analyze CCR5 polymorphism in diverse populations and its potential impact on HIV-1 subtype distribution.
  • To determine the relationship between viral phenotype, genotype, and coreceptor utilization.

Main Methods:

  • Examined coreceptor usage of 20 primary HIV-1 isolates representing subtypes A, B, C, D, E, and O.

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  • Sequenced 39 full-length CCR5 genes from individuals of diverse geographic origins.
  • Utilized peripheral blood mononuclear cells (PBMCs) to assess viral entry and coreceptor function.

    • Main Results:

    • CCR5 and CXCR4 are the primary coreceptors for all examined HIV-1 subtypes; CCR2b and CCR3 play minor roles.
    • Coreceptor usage is dictated by viral phenotype (NSI strains use CCR5, SI strains use CXCR4), not subtype genotype.
    • No significant geographic clustering of CCR5 polymorphism was observed, ruling it out as a driver of subtype distribution.

    Conclusions:

    • HIV-1 entry across diverse subtypes relies on CCR5 and CXCR4.
    • Viral phenotype is the primary determinant of coreceptor tropism.
    • Stochastic dissemination, rather than CCR5 diversity, likely explains the uneven global distribution of HIV-1 subtypes.