CC chemokine receptor 5 (CCR5) mediates activation of T lymphocytes and macrophages by functioning physiologically as a receptor for the leukocyte chemo-attractants macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and RANTES, as an important part of a protective immune response to injury and infection. Also, CCR5 functions pathologically as a key cell entry co-receptor for M-tropic strain of HIV-1 that is the primary transmitting form of the virus.
CCR5 has rapidly become the object of intense interest since the discovery of its role in the entry of HIV-1 into target cells. In contrast to that, one mutant allele, a 32-bp deletion (denoted DCCR5) in the open reading frame (ORF) of this gene, which has been intensively studied, was found to prevent cell invasion by HIV-1 virus. Individuals homozygous for this deletion do not express the protein on the cell surface, and are relatively resistant to developing HIV-1 infection, but this resistance appears not absolute, as isolated cases of HIV-positive deletion homozygotes are emerging. In contrast, individuals who display the heterozygous state (CCR5/DCCR5 genotype) can develop HIV-1 infection; however, their progression to AIDS may be slower.