Volume 3, Number 3—September 1997
Perspective
Host Genes and HIV: The Role of the Chemokine Receptor Gene CCR5 and Its Allele (∆32 CCR5)
Table 1
Ligands |
||||||
---|---|---|---|---|---|---|
(MCP-1Ra) Receptors (Old names)a | C-C chemokines | CXC chemokines | Predominant expression/Tissue distribution | Pathogensb | Chromosome location | GenBank Acc. # |
CC Receptors | ||||||
CCR1 (CC CKR1) | αβ, RANTES, MCP-3 | monocytes, T cells | 3p21 | L10918 | ||
CCR2A | MCP-1 | T cells, basophils, monocytes | 3p21 | U03882 | ||
CCR2B (MCP-1Rb) | MCP-1, 3, 4 | HIV-1 (NSI) | U03905 | |||
CCR3 (CKR3) | Eotaxin, RANTES, MCP-2,3,4 | eosinophil, basophils, microglial cells, and possibly monocytes; little expression in peripheral blood T-lymphocytes or dendritic cells | HIV-1 (NSI) | 3p21 | U28694 | |
CCR4 | TARC | basophils, T cells | 3p24 | X85740 | ||
CCR5c (CC CKR5) | RANTES, MIP-1αβ | monocytes, dendritic cells, microglial cells, T cells | HIV-1 (NSI), HIV-2 | 3p21 | U57840 | |
CXC Receptors | ||||||
CXCR1 (IL-8 RA) | IL-8 | neutrophils, NK cells | 2q35 | M68932 | ||
CXCR2 (IL-8 RB) | IL-8, MGSA, gro-α , NAP-2, IP-10, ENA-78, Mig | M73969 | ||||
CXCR3 | IP-10, Mig | activated T cells | X95876 | |||
CXCR4 (Fusin, LESTR, HUMSTR) | SDF-1 | wide: CD4+ and CD4- cells, monocytes, macrophages, dendritic cells, B cells; other tissues, e.g., brain, lung, spleen | HIV-1 (SI) HIV-2 | 2q21 | M99293 | |
CC/CXC Receptor | ||||||
DARC (Duffy antigen) | RANTES, MCP-1, TARC etc. | IL-8, MGSA, gro-α etc. | endothelial cells, erythrocytes | Plasmodium vivax | 1 | U01839 |
Othersd | ||||||
STRL33 | ND | ND | lymphoid tissues and activated T cells | HIV-1 | 3 | U73529 |
HCMV-US28 | MIP-1αβ, RANTES | fibroblasts infected with CMV | HIV-1 | N/A | X17403 | |
ChemR1 | ND | ND | T lymphocytes, polymorphonuclear cells | 3p21-24 | Y08456 | |
CMKBRL1 | ND | ND | neutrophils, monocytes, brain, liver, lung, skeletal muscles | 3p21 | U28934 | |
TER1 | ND | ND | thymus, spleen | 3p21 | U62556 | |
V28 | ND | ND | Neural and lymphoid tissue | 3p21 | U20350 | |
D2S201E | ND | ND | wide, including cells of hemopoietic origin | 2q21 | M99293 | |
BLR1 | ND | ND | B lymphocytes | X68149 | ||
EBI1 | ND | ND | B lymphocytes | L08176 | ||
GPR1,2,5 | ND | ND | ND | L36149 |
a New nomenclature for CC and CXC chemokine receptors was adopted at the Gordon Research Conference on Chemotactic Cytokines, June 23-28, 1996.
bPathogens using this receptor for infection.
cThe 32bp deleted allele of CCR5 has been referred to as CCR5-2 (19).
dChemokine receptor-like genes whose predicted proteins have 7 transmembrane domains.
Abbreviations: BLR1, Burkitt's lymphoma receptor-1; CMKBRL1, Chemokine β receptor like-1; DARC, duffy antigen/receptor for chemokines; EBI1, Epstein-Barr virus-induced receptor; ENA78, epithelial-derived neutrophil-activating peptide-78; GPR, G protein coupled receptor; gro, growth related gene product; HCMV, human cytomegalovirus; HUMSTR, human serum transmembrane segment receptor; IL, interleukin; IP-10, interferon-gamma inducible 10kD protein; LESTR, leukocyte-expressed seven-transmembrane-domain receptor; MCP, monocyte chemotactic protein; Mig, monokine induced by interferon gamma; MIP, macrophage inflammatory protein; NSI, non-syncytium inducing; N/A, not applicable; NAP-2, neutrophil-activating protein-2; ND, not determined; RANTES, regulated on activation, normal T cell expressed and secreted; SDF-1, stromal cell-derived factor-1; STRL33, seven transmembrane-domain receptor from lymphocyte clone 33; TARC, thymus and activation regulated chemokine.
References
- World Health Organization. Acquired immunodeficiency syndrome (AIDS)November 20, 1996. Wkly Epidemiol Rec. 1996;48:361.
- Steel CM, Ludlam CA, Beatson D, Peutherer JF, Cuthbert RJG, Simmonds P, HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease. Lancet. 1988;1:1185–8. DOIPubMedGoogle Scholar
- Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ, Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med. 1996;2:405–11. DOIPubMedGoogle Scholar
- McNeil AJ, Yap PL, Gore SM, Brettle RP, McCol M, Wyld R, Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease. QJM. 1996;89:177–85.PubMedGoogle Scholar
- Malkovsky M. HLA and natural history of HIV infection. Lancet. 1996;348:142–3. DOIPubMedGoogle Scholar
- Rowland-Jones S, Sutton J, Ariyoshi K, Dong T, Gotch F, McAdam S, HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat Med. 1995;1:59–64. DOIPubMedGoogle Scholar
- Paxton WA, Martin SR, Tse D, O'Brient TR, Skurnick J, VanDevanter NL, Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nat Med. 1996;2:412–7. DOIPubMedGoogle Scholar
- Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, . Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86:367–77. DOIPubMedGoogle Scholar
- Fowke KR, Nagelkerke NJD, Kimani J, Simonsen JN, Anzala AO, Bwayo JJ, Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya. Lancet. 1996;348:1347–51. DOIPubMedGoogle Scholar
- Stephens H, Beyrer C, Mastro T, Nelson KE, Klaythong R, Kunachiwa W, HLA class I alleles in a cohort of HIV-1 exposed, persistently seronegative (HEPS) sex workers (CSWs) in Northern Thailand. In: Proceedings of the 3rd Conference on Retroviruses and Opportunistic Infections; 1996 January. Washington (DC): American Society for Microbiology; 1996.
- Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996;2:1240–3. DOIPubMedGoogle Scholar
- Fowke K, Slaney LA, Simonsen JN, Nagelkerke N, Nath A, Anzala AO, HIV-1 resistant prostitutes: an innate mechanism. In: Proceedings of the 1st National Conference on Human Retroviruses; Dec 12-16. Washington (DC): American Society for Microbiology; 1993; p. 82.
- Plummer FA, Fowke K, Nagelkerke NDJ, Simonsen JN, Bwayo J, Ngugi E, Evidence of resistance to HIV among continuously exposed prostitutes in Nairobi, Kenya. In: Abstracts of the 9th International Conference on AIDS; Berlin 1993 June 6-11; WS-A07-3. Sponsored by the International AIDS Society and World Health Organization.
- Rowland-Jones SL, McMichael A. Immune responses in HIV-exposed seronegatives: have they repelled the virus? Curr Opin Immunol. 1995;7:448–55. DOIPubMedGoogle Scholar
- Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382:722–5. DOIPubMedGoogle Scholar
- Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Genetic restriction of HIV-1 infection and progression to AIDS by a deletion of the CKR5 structural gene. Science. 1996;273:1856–62. DOIPubMedGoogle Scholar
- Michael NL, Chang G, Louie LG, Mascola JR, Dondero D, Birx DL, The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression. Nat Med. 1997;3:338–40. DOIPubMedGoogle Scholar
- Zimmerman PA, Bucklerwhite A, Alkhatib G, Spalding T, Kubofcik J, Combadiere C. Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5--studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk. Mol Med. 1997;3:23–36.PubMedGoogle Scholar
- Biti R, Ffrench R, Young J, Bennetts B, Stewart G. HIV-1 infection in an individual homozygous for the CCR5 deletion allele. Nat Med. 1997;3:252–3. DOIPubMedGoogle Scholar
- O'Brien TR, Winkler C, Dean M, Nelson JAE, Carrington M, Michael NL, HIV-1 infection in a man homozygous for CCR5 ∆32. Lancet. 1997;349:1219. DOIPubMedGoogle Scholar
- Theodorou I, Meyer L, Magierowska M, Katlama C, Rouzious C; Seroco Study Group. HIV-1 infection in an individual homozygous for CCR5 ∆32. Lancet. 1997;349:1219–20. DOIPubMedGoogle Scholar
- Eugen-Olsen J, Iversen AKN, Garred P, Koppelhus U, Pedersen C, Benfield TL, Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. AIDS. 1997;11:305–10. DOIPubMedGoogle Scholar
- Garred P, Madsen HO, Balslev U, Hofmann B, Gerstoft J, Svejgaard A. Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet. 1997;349:236–40. DOIPubMedGoogle Scholar
- Brinkman BMN, Keet IPM, Miedema F, Verweij CL, Klein M. Polymorphisms within the human tumor necrosis factor-a promoter region in human immunodeficiency virus type 1-seropositive persons. J Infect Dis. 1997;375:188–90.
- Khoo SH, Pepper L, Snowden N, Hajeer AH, Vallely P, Wilkins EG, Tumor necrosis factor c2 microsatellite allele is associated with the rate of HIV disease progression. AIDS. 1997;11:423–8. DOIPubMedGoogle Scholar
- Murphy PM. Chemokine receptors: structure, function and role in microbial pathogenesis. Cytokine Growth Factor Rev. 1996;7:47–64. DOIPubMedGoogle Scholar
- Napolitano M, Zingoni A, Bernardini G, Spinetti G, Nista A, Storlazzi C, Molecular cloning of TER1, a chemokine receptor-like gene expressed by lymphoid tissues. J Immunol. 1996;157:2759–63.PubMedGoogle Scholar
- Miller LH. Impact of malaria on genetic polymorphism and genetic diseases in Africans and African Americans. Proc Natl Acad Sci U S A. 1997;91:2415–9. DOIGoogle Scholar
- Tournamille C, Colin Y, Cartron JP, Le Van Kim C. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet. 1995;10:224–8. DOIPubMedGoogle Scholar
- Pleskoff O, Treboute C, Brelot A, Heveker N, Seman M, Alizon M. Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science. 1997;276:1874–8. DOIPubMedGoogle Scholar
- Cocchi F, DeVico AL, Garzine-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1a and MIPß as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995;270:1811–5. DOIPubMedGoogle Scholar
- Deng HK, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Identification of a major coreceptor for primary isolates of HIV-1. Nature. 1996;381:661–6. DOIPubMedGoogle Scholar
- Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactorfunctional CDNA cloning of seventransmembrane, G protein-coupled receptor. Science. 1996;272:872–7. DOIPubMedGoogle Scholar
- Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996;35:3362–6. DOIPubMedGoogle Scholar
- Dragic T, Litwin V, Allaway GP, Martin SR, Huang YX, Nagashima KA, HIV-1 entry into CD4(+) cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996;381:667–73. DOIPubMedGoogle Scholar
- Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, CC CKRSA RANTES, MIP-1-α, MIP-1ß receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–8. DOIPubMedGoogle Scholar
- Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, The ß-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996;85:1135–48. DOIPubMedGoogle Scholar
- Doranz BJ, Rucker J, Yi YJ, Smyth RJ, Samson M, Peiper SC, A dual-tropic primary HIV-1 isolate that uses fusin and the ß-chemokine receptors CKR-5, CKR-3 and CKR-2b as fusion cofactors. Cell. 1996;85:1149–58. DOIPubMedGoogle Scholar
- He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature. 1997;385:645–9. DOIPubMedGoogle Scholar
- Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A. 1997;94:1925–30. DOIPubMedGoogle Scholar
- Simmons G, Wilkinson D, Reeves JD, Dittmar MT, Beddows S, Weber J, Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either lestr or CCR5 as coreceptors for virus entry. J Virol. 1996;70:8355–60.PubMedGoogle Scholar
- Zhang L, Huang Y, He T, Cao Y, Ho DD. HIV-1 subtype and second-receptor use. Nature. 1996;383:768. DOIPubMedGoogle Scholar
- Cocchi F, DeVico AL, Garzino-Demo A, Cara A, Gallo RC, Lusso P. The V3 domain of the HIV-1 gp 120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nat Med. 1996;2:1244–7. DOIPubMedGoogle Scholar
- Wu L, Gerard NP, Wyatt R, Choe H, Parolin C, Ruffing N, CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature. 1996;384:179–83. DOIPubMedGoogle Scholar
- Trkola A, Dragic T, Arthos J, Binley JM, Olson WC, Allaway GP, CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR5. Nature. 1996;384:184–7. DOIPubMedGoogle Scholar
- Rucker J, Samson M, Doranz BJ, Libert F, Berson JF, Yi Y, Regions in ß-chemokine receptors CCR5 and CCR2b that determine HIV-1 cofactor specificity. Cell. 1996;87:437–46. DOIPubMedGoogle Scholar
- Atchison RE, Gosling J, Monteclaro FS, Franci C, Digilio L, Charo IF, Multiple extracellular elements of CCR5 and HIV-1: dissociation from response to chemokines. Science. 1996;274:1924–6. DOIPubMedGoogle Scholar
- Lapham C, Ouyang J, Chandrasekhar B, Nguyen N, Dimitrov D, Golding H. Evidence for cell-surface association between fusin and the CD4-gp 120 complex in human cell lines. Science. 1996;274:602–5. DOIPubMedGoogle Scholar
- Oravecz T, Pall M, Norcross MA. ß-Chemokine inhibition of monocytotropic HIV-1 infection. Interference with a postbinding fusion step. J Immunol. 1996;157:1329–32.PubMedGoogle Scholar
- Paxton WA, Dragic T, Koup RA, Moore JP. Perspective--research highlights at the Aaron Diamond AIDS Research Center--the beta-chemokines, HIV type 1 second receptors, and exposed uninfected persons. AIDS Res Hum Retroviruses. 1996;12:1203–7. DOIPubMedGoogle Scholar
- Wu L, Paxton WA, Kassam N, Ruffing N, Rottman JB, Sullivan N, CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med. 1997;185:1681–91. DOIPubMedGoogle Scholar
- Kaslow RA, Koup R, Zimmerman P, Dean M, Naik E, Enger C, HLA scoring profile (HSP) and CCR5 deletion heterozygosity as predictors of AIDS in seroconverters. In: Proceedings of the 4th Conference on Retroviruses and Opportunistic Infections; Jan 22-26. Washington (DC): American Society of Microbiology: 1997; p. 69.
- Combadiere C, Ahuja SK, Murphy PM. Cloning and functional expression of a human eosinophil CC chemokine receptor. J Biol Chem. 1996;271:11034.PubMedGoogle Scholar
- Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med. 1996;183:2349–54. DOIPubMedGoogle Scholar
- Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med. 1996;183:2437–48. DOIPubMedGoogle Scholar
- D'Souza MP, Harden VA. Chemokines and HIV-1 second receptors. Nat Med. 1996;2:1293–300. DOIPubMedGoogle Scholar
- Kolata G. New AIDS study reveal startling immunity data. The New York Times. 1996; September 27, 1996. p. A13.
- Kolata G. Geneticists seek to understand why disease genes spread. The New York Times 1996; Sect. B:5-9.
- Easterbrook PJ, Chmiel JS, Hoover DR, Saah AJ, Kaslow RA, Kingsley LA, Racial and ethnic differences in human immunodeficiency virus type 1 (HIV-1) seroprevalence among homosexual and bisexual men.The multicenter AIDS cohort study. Am J Epidemiol. 1993;138:415–29.PubMedGoogle Scholar
- Soto-Ramirez LE, Renjifo B, McLane MF, Marlink R, O'Hara C, Sutthent R, HIV-1 Langerhans' cell tropism associated with heterosexual transmission of HIV. Science. 1996;271:1291–3. DOIPubMedGoogle Scholar
1Garred P, Eugen-Olsen J, Iversen AKN, Benfield TL, Svejgaard A, Hofmann, B, the Copenhagen AIDS Study Group. Dual effect of CCR5 D32 gene deletion in HIV-1-infected patients. Lancet 1997; 349:1884.
2Martinson JJ, Chapman NH, Rees DC, Lui Y-T, Clegg JB. Global distribution of the CCR5 gene 32-basepair deletion [letter]. Nature Genetics 1997;16:100-103.
3Centers for Disease Control and Prevention. Facts about CCR5 and protection against HIV-1 infection; 1997.