Chemokine (C-C motif) receptor 5 (gene/pseudogene)
Rendering based on PDB 1ND8.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L87, 2RLL, 2RRS
Identifiers
Symbols	CCR5; CC-CKR-5; CCCKR5; CCR-5; CD195; CKR-5; CKR5; CMKBR5; IDDM22
External IDs	OMIM: 601373 MGI: 107182 HomoloGene: 37325 IUPHAR: CCR5 ChEMBL: 274 GeneCards: CCR5 Gene
Gene Ontology Molecular function • actin binding • phosphatidylinositol phospholipase C activity • signal transducer activity • receptor activity • G-protein coupled receptor activity • chemokine receptor activity • protein binding • coreceptor activity • C-C chemokine receptor activity • C-C chemokine receptor activity • C-C chemokine binding • chemokine (C-C motif) ligand 5 binding Cellular component • cytoplasm • endosome • plasma membrane • integral to plasma membrane • external side of plasma membrane • cell surface Biological process • MAPK cascade • dendritic cell chemotaxis • calcium ion transport • chemotaxis • inflammatory response • immune response • cellular defense response • cell surface receptor signaling pathway • G-protein coupled receptor signaling pathway • elevation of cytosolic calcium ion concentration • cell-cell signaling • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum • viral reproduction • initiation of viral infection • calcium-mediated signaling • signaling • entry into host cell • interspecies interaction between organisms • response to cholesterol • cellular response to lipopolysaccharide Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1234	12774
Ensembl	ENSG00000160791	ENSMUSG00000079227
UniProt	P51681	P51682
RefSeq (mRNA)	NM_000579.3	NM_009917.5
RefSeq (protein)	NP_000570.1	NP_034047.2
Location (UCSC)	Chr 3: 46.41 – 46.42 Mb	Chr 9: 124.04 – 124.06 Mb
PubMed search	[1]	[2]
This box: view talk edit

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation known as CCR5 delta 32 in the CCR5 gene, protecting them against these strains of HIV.

In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the genetic deletion of a portion of the CCR5 gene. Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.^[1]

Function[link]

The CCR5 protein belongs to the beta chemokine receptors family of integral membrane proteins.^[2][3] It is a G protein-coupled receptor^[2] which functions as a chemokine receptor in the CC chemokine group.

The natural chemokine ligands that bind to this receptor are RANTES (a chemotactic cytokine protein also known as CCL5)^[4][5][6] and macrophage inflammatory protein (MIP) 1α and 1β (also known as CCL3 and CCL4). It also interacts with CCL3L1.^[5][7]

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[link]

Attachment of HIV to a CD4+ T-helper cell: 1) the gp120 viral protein attaches to CD4. 2) gp120 variable loop attaches to a coreceptor, either CCR5 or CXCR4. 3) HIV enters the cell.

HIV most commonly uses CCR5 and/or 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,^[8] 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 CCR5 receptor antagonists, 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.

CCR5-Δ32[link]

CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a genetic variant of CCR5.^[9][10]

CCR5-Δ32 is a deletion mutation of a gene that has a specific impact on the function of T cells.^{[citation needed]} At least one copy of CCR5-Δ32 is found in about 10% of people of Northern Europe and in those of Northern European descent. It has been hypothesized that this allele was favored by natural selection during the Black Death. This coalescence date is contradicted by purported evidence of CCR5-Δ32 in Bronze Age samples, at levels comparable to the modern European population.^[11] Smallpox may be another candidate for the high level of the mutation in the European population.^[9]

The allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV. Yersinia pestis (the bubonic plague bacterium) was demonstrated in the laboratory not to 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,^[12] indicating that not all of the functions of CCR5 may 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.^[13] This allele is found in 5–14% of Europeans but is rare in Africans and Asians.^[14] 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. 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 two years. 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.^[15]

A genetic approach involving intrabodies that block CCR5 expression has been proposed as a treatment for HIV-1 infected individuals.^[16] When T-cells modified so they no longer express CCR5 were mixed with unmodified T-cells expressing CCR5 and then challenged by infection with HIV-1, the modified T-cells that do not express CCR5 eventually take over the culture, as HIV-1 kills the non-modified T-cells. This same method might be used in vivo to establish a virus resistant cell pool in infected individuals.^[16]

This hypothesis was tested in an AIDS patient who had also developed myeloid leukemia, and was treated with chemotherapy to suppress the cancer. A bone marrow transplant containing stem cells from a matched donor was then used to restore the immune system. However, the transplant was performed from a donor with 2 copies of CCR5-Δ32 mutation gene. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues.^[17][18] Before the transplant, low levels of HIV X4, which does not use the CCR5 receptor, were also detected. Following the transplant, however, this type of HIV was not detected either, further baffling doctors.^[18] However, this is consistent with the observation that cells expressing the CCR5-Δ32 variant protein lack both the CCR5 and CXCR4 receptors on their surfaces, thereby conferring resistance to a broad range of HIV variants including HIV X4.^[19] After three years, the patient has maintained the resistance to HIV and has been pronounced cured of the HIV infection.^[20]

Enrollment of HIV-positive patients in a clinical trial was started in 2009 in which the patients' cells were genetically modified with a zinc finger nuclease to carry the CCR5-Δ32 trait and then reintroduced into the body as a potential HIV treatment.^[21][22]

See also[link]

• Discovery and development of CCR5 receptor antagonists
• Entry inhibitor
• HIV tropism

References[link]

Further reading[link]

External links[link]

• Video and text from a PBS documentary about the discovery of CCR5
• "Chemokine Receptors: CCR5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2228. 
• HuGENavigator literature on HIV Infections and CCR5 from CDC - (note, authors may not be CDC employees, and there is no public domain notice on the page, so this cannot be assumed to be public domain)
• Schering-Plough Initiates Phase III Studies with CCR5-Vicriviroc in Treatment- Experienced HIV Patients.

This biographical article needs additional citations for verification. Please help by adding reliable sources. Contentious material about living persons that is unsourced or poorly sourced must be removed immediately, especially if potentially libelous or harmful. (October 2009)

This article or section reads like a news release, or is otherwise written in an overly promotional tone. Please help by either rewriting this article from a neutral point of view or by moving this article to Wikinews. When appropriate, blatant advertising may be marked for speedy deletion with {{db-spam}}. (August 2010)

Christian Scott
Christian Scott performing iin 2009
Background information
Birth name	Christian Scott
Born	(1983-03-31) 31 March 1983 (age 29) New Orleans, Louisiana United States
Genres	Jazz, rock
Occupations	Musician, arranger, composer, record producer
Instruments	Trumpet, flugelhorn, cornet, slide trumpet
Years active	1996-present
Labels	Concord, Universal
Associated acts	The Christian Scott Quintet, Donald Harrison, Jr. Quartet, McCoy Tyner, Mos Def, Marcus Miller, Prince
Website	www.christianscott.tv

Christian Scott, born March 31, 1983, in New Orleans, Louisiana, is the 2010 Edison Award winner for Best International Jazz Artist and a Grammy Award-nominated jazz trumpeter, composer and producer. He has been heralded by JazzTimes magazine as "the Architect of a new commercially viable fusion" and "Jazz's young style God".^[1]

The nephew of jazz alto saxophonist Donald Harrison,^[2] since 2006 Scott has released four studio albums, and one live recording.

The trumpeter is noted for his use of an unvoiced tone, which he calls his "whisper technique."^[3]