Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene

Nature. 1996 Aug 22;382(6593):722-5. doi: 10.1038/382722a0.

Abstract

HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • Cohort Studies
  • DNA Primers
  • European Continental Ancestry Group / genetics
  • Frameshift Mutation*
  • Gene Frequency
  • Genotype
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Seropositivity / genetics
  • HIV Seropositivity / immunology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Membrane Fusion
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Conformation
  • Receptors, CCR5
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology*
  • Receptors, HIV / chemistry
  • Receptors, HIV / genetics
  • Receptors, HIV / immunology*

Substances

  • DNA Primers
  • Receptors, CCR5
  • Receptors, Cytokine
  • Receptors, HIV

Associated data

  • GENBANK/X99393