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(1997) showed by immunohistochemistry and flow cytometry that CCR5 is expressed by bone marrow-derived cells known to be targets for HIV-1 infection, including a subpopulation of lymphocytes and monocytes/macrophages in blood, primary and secondary lymphoid organs, and noninflamed tissues.
In the central nervous system, CCR5 was expressed on neurons, astrocytes, and microglia.
In transfected cells, macrophage inflammatory protein (MIP)-1-alpha (182283) appeared to be the most potent agonist for CCCKR5, with MIP-1-beta (CCL4; 182284) and RANTES (CCL5; 187011) also active at physiologic concentrations. (1996) detected transcript from the gene in a promyeloblastic cell line, which suggested a potential role for the chemokine receptor in granulocyte lineage proliferation and differentiation. (1996) showed that MIP-1-alpha, MIP-1-beta, and RANTES each inhibit infection of CD4 cells by primary, nonsyncytium-inducing (NSI) HIV-1 strains at the virus entry stage and also block env-mediated cell-cell fusion.
Both groups showed that expression of the CCCKR5 protein renders nonpermissive CD4 cells susceptible to infection by HIV-1 strains (see 609423).
(2000) presented results indicating that amino acids 2-18 of the CCR5 amino-terminal domain compose a gp120-binding site that determines specificity of the interaction between CCR5 and gp120s from 2 HIV-1 isolates.
This protection is related to homozygous mutations in CCR5, the receptor for the beta-chemokines, and earlier studies had shown that the same chemokines markedly suppressed the nonsyncytial inducing variants of HIV-1, the chief virus type transmitted from person to person.
However, CCR5 mutations are not likely to be the unique mechanism of protection because HIV-1 variants can use other chemokine receptors as their coreceptor and, indeed, infection has been demonstrated within the presence of such mutations.
With a set of overlapping lambda clones, they showed that the gene is 17.5 kb from the CMKBR2 gene (CCR2; 601267).
The 2 coding regions share 75% DNA and amino acid sequence identity. (1997) analyzed the genomic structure of CCR5, which contains 4 exons, spanning approximately 6 kb, and only 2 introns. Exon 4 contains the open reading frame, the complete 3-prime UTR, and 11 nucleotides of the 5-prime UTR.
Furthermore, and remarkably, 14 subjects remained unaffected to the time of the report, and in these subjects homozygous CCR5 mutations were found in none, but in most of them there was overproduction of beta-chemokines.