Detection of Polymorphisms in the HIV-1 Coreceptor CCR5 Using Single-Strand Conformation Polymorphism

The CCR5 gene encodes a cell-surface chemokine receptor molecule, which serves as a coreceptor for macrophage-tropic strains of HIV-1 (1-3). Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding or HIV-1 infection of cells on which the receptor is normally expressed. Indeed, it was recently shown that individuals homozygous for a mutant allele (CCR5-△32) characterized by a 32-bp deletion in the coding region of the CCR5 gene, are relatively resistant to HIV-1 infection (4-6). This allele causes a frame shift at amino acid 185, and homozygous individuals fail to express detectable cell-surface CCR5 molecules. It is possible that other as-yet unidentified variants play a role in HIV-1 infectivity and outcome. Several additional mutations, most of which are single-base substitutions, have been identified in the coding region of the CCR5 gene using the single-strand conformation polymorphism (SSCP) technique (7).