Chemokine (C-C motif) receptor 5
Identifiers
Symbol(s)	CCR5; CC-CKR-5; CCCKR5; CD195; CKR-5; CKR5; CMKBR5
External IDs	OMIM: 601373 MGI: 107182 HomoloGene: 37325
Orthologs
	Human	Mouse
Entrez	1234	12774
Ensembl	n/a	ENSMUSG00000073993
Uniprot	n/a	Q3TDA4
Refseq	NM_000579 (mRNA) NP_000570 (protein)	NM_009917 (mRNA) NP_034047 (protein)
Location	n/a	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 Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles Chemokine receptors are Cytokine receptors found on the surface of certain cells which interact with a type of Cytokine called a Chemokine. The natural chemokines that bind to this receptor are RANTES, MIP-1α and MIP-1β. Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics CCL5 (earlier called RANTES) is an 8kDa Protein classified as a chemotactic Cytokine or Chemokine. Macrophage Inflammatory Proteins (MIP belong to the family of chemotactic Cytokines known as Chemokines In humans there are two major forms MIP-1α CCR5 is also the name of the gene that codes for the CCR5 receptor. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance It is located on chromosome 3 on the short (p) arm at position 21. 125px|right Chromosome 3 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. Microglia are a type of Glial cell that acts as the first and main form of active immune defense in the Central nervous system (CNS It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear.

CCR5 has also recently been designated CD195 (cluster of differentiation 195). The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes

Contents 1 HIV 2 CCR5-Δ32 3 References 4 Further reading 5 External links

HIV

HIV uses CCR5 or another protein, CXCR4, as a co-receptor to enter its target cells. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome CXCR4, (a '''CXC''' chemokine '''R'''eceptor) also called fusin, is an alpha- Chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate Ligand recognition and initiate 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 Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally CCL5 (earlier called RANTES) is an 8kDa Protein classified as a chemotactic Cytokine or Chemokine. Chemokine (C-C motif ligand 4, also known as CCL4, is a human Gene. Chemokine (C-C motif ligand 3, also known as CCL3, is a human Gene. 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). PRO 140 is a humanized Monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human Immune system. Vicriviroc, previously named SCH 417690 and SCH-D is a pyrimidine currently undergoing clinical trials as a CCR5 Entry inhibitor of HIV-1. Schering-Plough Corporation ( is a Pharmaceutical company founded in 1851 by Ernst Schering as Schering AG in Germany. GlaxoSmithKline plc () is a United Kingdom -based pharmaceutical, biological and Healthcare Company. Maraviroc (brand-named Selzentry, or Celsentri outside the US Pfizer Incorporated ( is a major Pharmaceutical company, which ranks number one in the world in sales 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. A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks Development of Aplaviroc has been terminated due to safety concerns (potential liver toxicity). ^[1]

Further information: HIV Tropism and Entry inhibitors

CCR5-Δ32

CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a genetic variant of CCR5. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome ^{[2] [3]}

It is a deletion mutation of a gene that has a specific impact on the function of T cells. In Genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) is a Mutation (a genetic aberration T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. CCR5-Δ32 is widely dispersed throughout Northern Europe and in those of Northern European descent. The European peoples are the various Nations and Ethnic groups of Europe. It has been hypothesized that this allele was favored by natural selection during the Black Death, or during smallpox outbreaks, but this is unlikely, given that the frequency of CCR5-Δ32 in Bronze Age samples is similar to that seen today. An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms Natural selection is the process by which favorable Heritable traits become more common in successive Generations of a Population of The Black Death, or the Black Plague, was one of the deadliest Pandemics in human history widely thought to have been caused by a bacterium named Yersinia Smallpox is an Infectious disease unique to humans caused by either of two virus variants named Variola major and Variola minor. ^[4] The allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV. Smallpox is an Infectious disease unique to humans caused by either of two virus variants named Variola major and Variola minor. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Yersinia pestis was demonstrated in the laboratory to not associate with CCR5. Individuals with the Δ32 allele of CCR5 are healthy, suggesting that CCR5 is largely dispensable. However, CCR5 apparently plays a role in mediating resistance to West Nile virus infection in humans, as CCR5-Δ32 individuals have shown to be disproportionately at higher risk of West Nile virus in studies ^[5], indicating that all of the functions of CCR5 may not be compensated by other receptors. West Nile virus (or WNV is a Virus of the family Flaviviridae; part of the Japanese encephalitis (JE antigenic complex of viruses it is found in

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. The European peoples are the various Nations and Ethnic groups of Europe. The term African people can refer to people who live in Africa, or people who trace their ancestry to Indigenous inhabitants of Africa. Asian or Asiatic is a Demonym for people from Asia. However the use of the term varies by country and person often referring to people from a particular ^[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. Following infection with HIV -1 the rate of clinical disease progression varies between individuals It is possible that a person with the CCR5-Δ32 receptor allele will not be infected with HIV R5 strains. Several commercial testing companies offer tests for CCR5-Δ32.

Further information: Long-term nonprogressors

References

Further reading

External links

• Video and text from a PBS documentary about the discovery of CCR5
• IUPHAR GPCR Database - CCR5 Chemokine Receptor
• fact sheet: CCR5 receptor gene and HIV infection at CDC - (note, author is not a CDC employee, and there is no public domain notice on the page, so this cannot be assumed to be public domain)
• http://www.cdc.gov/genomics/hugenet/factsheets/FS_CCR5.htm 2% African American show CCR5 indicating extremely recent origin. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated The public domain is a range of abstract materials &ndash commonly referred to as Intellectual property &ndash which are not owned or controlled by anyone Smallpox initiator suspect.
• Schering-Plough Initiates Phase III Studies with CCR5-Vicriviroc in Treatment- Experienced HIV Patients.

---

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic