My watch list  


Chemokine (C-C motif) receptor 5
Symbol(s) CCR5; CC-CKR-5; CCCKR5; CD195; CKR-5; CKR5; CMKBR5
External IDs OMIM: 601373 MGI: 107182 Homologene: 37325
Human Mouse
Entrez 1234 12774
Ensembl na ENSMUSG00000073993
Uniprot na Q3TDA4
Refseq NM_000579 (mRNA)
NP_000570 (protein)
NM_009917 (mRNA)
NP_034047 (protein)
Location na Chr 9: 123.97 - 123.98 Mb
Pubmed search [1] [2]

CCR5, short for chemokine (C-C motif) receptor 5, is a chemokine receptor. The natural chemokines that bind to this receptor are RANTES, MIP-1α and MIP-1β. CCR5 is also the name of the gene that codes for the CCR5 receptor. It is located on chromosome 3 on the short (p) arm at position 21. CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear.



HIV uses CCR5 or another protein, CXCR4, as a co-receptor to enter its target cells. Several chemokine receptors can function as viral coreceptors, but CCR5 is likely the most physiologically important coreceptor during natural infection. The normal ligands for this receptor, RANTES, MIP-1β and MIP-1α, are able to suppress HIV-1 infection in vitro. In individuals infected with HIV, CCR5-using viruses are the predominant species isolated during the early stages of viral infection, suggesting that these viruses may have a selective advantage during transmission or the acute phase of disease. Moreover, at least half of all infected individuals harbor only CCR5-using viruses throughout the course of infection.

A number of new experimental HIV drugs, called entry inhibitors, have been designed to interfere with the interaction between CCR5 and HIV, including PRO140 (Progenics), Vicriviroc (Schering Plough), Aplaviroc (GW-873140) (GlaxoSmithKline) and Maraviroc (UK-427857) (Pfizer). A potential problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another coreceptor (CXCR4) but persisted in using CCR5, either through binding to alternative domains of CCR5, or by binding to the receptor at a higher affinity. Development of Aplaviroc has been terminated due to safety concerns (potential liver toxicity). [1]

Further information: HIV Tropism and Entry inhibitors


CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a genetic variant of CCR5.[2] [3]

It is a deletion mutation of a gene that has a specific impact on the function of T cells. CCR5-Δ32 is widely dispersed throughout Northern Europe and in those of European descent. It has been hypothesized that this allele was favored by natural selection during the Black Death, or during smallpox outbreaks, which is unlikely, given that the frequency of CCR5-Δ32 in Bronze Age samples is similar to that seen today.[4] The allele has a negative effect upon T cell function, but appears to protect against smallpox, plague and HIV. Individuals with the Δ32 allele of CCR5 are healthy, suggesting that CCR5 is largely dispensable. However, CCR5 plays a role in mediating resistance to West Nile virus infection in humans, as CCR5-Δ32 individuals are enriched in cohorts of West Nile virus symptomatic patients [5], indicating that all of the functions of CCR5 may not be compensated by other receptors.

While CCR5 has multiple variants in its coding region, the deletion of a 32-bp segment results in a nonfunctional receptor, thus preventing HIV R5 entry; two copies of this allele provide strong protection against HIV infection.[6] This allele is found in 5-14% of Europeans but is rare in Africans and Asians.[7] Multiple studies of HIV-infected persons have shown that presence of one copy of this allele delays progression to the condition of AIDS by about 2 years. CCR5-Δ32 decreases the number of CCR5 proteins on the outside of the CD4 cell, which can have a large effect on the HIV disease progression rates. It is possible that a person with the CCR5-Δ32 receptor allele will not be infected with HIV R5 strains.

Further information: Long-term nonprogressors


  1. ^
  2. ^ Galvani A, Slatkin M (2003). "Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele". Proc Natl Acad Sci U S A 100 (25): 15276-9. PMID 14645720.
  3. ^ Stephens J et al (1998). "Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes". Am J Hum Genet 62 (6): 1507-15. PMID 9585595.
  4. ^ Philip W. Hedrick; Brian C. Verrelli (Jun 2006). "‘Ground truth’ for selection on CCR5-Δ32". Trends in Genetics 22 (6): 293-6. PMID 16678299.
  5. ^;203/1/35
  6. ^ Biologists discover why 10 percent of Europeans are safe from HIV infection. (Mar 2005). Retrieved on 2007-04-10.
  7. ^ Pardis C. Sabeti; Emily Walsh, Steve F. Schaffner, Patrick Varilly, Ben Fry, Holli B. Hutcheson, Mike Cullen, Tarjei S. Mikkelsen, Jessica Roy, Nick Patterson, Richard Cooper, David Reich, David Altshuler, Stephen O’Brien, Eric S. Lander (Nov 2005). "The case for selection at CCR5-Delta32". PLoS Biology 3 (11): e378. PMID 16248677.

Further reading

  • Wilkinson D (1997). "Cofactors provide the entry keys. HIV-1.". Curr. Biol. 6 (9): 1051-3. PMID 8805353.
  • Broder CC, Dimitrov DS (1997). "HIV and the 7-transmembrane domain receptors.". Pathobiology 64 (4): 171-9. PMID 9031325.
  • Choe H, Martin KA, Farzan M, et al. (1998). "Structural interactions between chemokine receptors, gp120 Env and CD4.". Semin. Immunol. 10 (3): 249-57. PMID 9653051.
  • Sheppard HW, Celum C, Michael NL, et al. (2002). "HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion.". J. Acquir. Immune Defic. Syndr. 29 (3): 307-13. PMID 11873082.
  • Freedman BD, Liu QH, Del Corno M, Collman RG (2004). "HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages.". Immunol. Res. 27 (2-3): 261-76. PMID 12857973.
  • Esté JA (2004). "Virus entry as a target for anti-HIV intervention.". Curr. Med. Chem. 10 (17): 1617-32. PMID 12871111.
  • Gallo SA, Finnegan CM, Viard M, et al. (2003). "The HIV Env-mediated fusion reaction.". Biochim. Biophys. Acta 1614 (1): 36-50. PMID 12873764.
  • Zaitseva M, Peden K, Golding H (2003). "HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral-cell fusion and as targets for entry inhibitors.". Biochim. Biophys. Acta 1614 (1): 51-61. PMID 12873765.
  • Lee C, Liu QH, Tomkowicz B, et al. (2004). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways.". J. Leukoc. Biol. 74 (5): 676-82. doi:10.1189/jlb.0503206. PMID 12960231.
  • Yi Y, Lee C, Liu QH, et al. (2004). "Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: Implications for neuropathogenesis.". J. Neurovirol. 10 Suppl 1: 91-6. PMID 14982745.
  • Seibert C, Sakmar TP (2004). "Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs.". Curr. Pharm. Des. 10 (17): 2041-62. PMID 15279544.
  • Cutler CW, Jotwani R (2006). "Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of resistance or susceptibility to HIV infection?". Adv. Dent. Res. 19 (1): 49-51. PMID 16672549.
  • Ajuebor MN, Carey JA, Swain MG (2006). "CCR5 in T cell-mediated liver diseases: what's going on?". J. Immunol. 177 (4): 2039-45. PMID 16887960.
  • Lipp M, Müller G (2006). "Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking.". Verhandlungen der Deutschen Gesellschaft für Pathologie 87: 90-101. PMID 16888899.
  • Balistreri CR, Caruso C, Grimaldi MP, et al. (2007). "CCR5 receptor: biologic and genetic implications in age-related diseases.". Ann. N. Y. Acad. Sci. 1100: 162-72. doi:10.1196/annals.1395.014. PMID 17460174.
  • Madsen HO, Poulsen K, Dahl O, et al. (1990). "Retropseudogenes constitute the major part of the human elongation factor 1 alpha gene family.". Nucleic Acids Res. 18 (6): 1513-6. PMID 2183196.
  • Uetsuki T, Naito A, Nagata S, Kaziro Y (1989). "Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha.". J. Biol. Chem. 264 (10): 5791-8. PMID 2564392.
  • Whiteheart SW, Shenbagamurthi P, Chen L, et al. (1989). "Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha.". J. Biol. Chem. 264 (24): 14334-41. PMID 2569467.
  • Ann DK, Wu MM, Huang T, et al. (1988). "Retinol-regulated gene expression in human tracheobronchial epithelial cells. Enhanced expression of elongation factor EF-1 alpha.". J. Biol. Chem. 263 (8): 3546-9. PMID 3346208.
  • Brands JH, Maassen JA, van Hemert FJ, et al. (1986). "The primary structure of the alpha subunit of human elongation factor 1. Structural aspects of guanine-nucleotide-binding sites.". Eur. J. Biochem. 155 (1): 167-71. PMID 3512269.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "CCR5". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE