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 2
aCCR5 Genotypes % (N) |
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Author | Population | Ethnicity | HIV Status | No. | W/W | w/∆32 | ∆32/∆32 | ∆32 allele frequency (%) |
Liu et al. (9) | High-risk, USA | Caucasian | Neg | 15 | 80.0 (12) | 0 (0) | 20.0 (3) | 0.200 |
General, USA | Caucasian | Neg | 122 | 80.3 (98) | 19.7 (24) | 0 (0) | 0.098 | |
General, S. America | Venezuelan | Neg | 46 | 100 (46) | 0 (0) | 0 (0) | 0 | |
Samson et al. (16) | General, Europe | Caucasian | Neg | 704 | 82.7 (582) | 16.2 (114) | 1.1 (8) | 0.092 |
General, Asia | Japanese | Neg | 248 | 100 (248) | 0 (0) | 0 (0) | 0 | |
General, Africa | Ctrl/West African | Neg | 124 | 100 (124) | 0 (0) | 0 (0) | 0 | |
AIDS clinics, Paris | Caucasian | Pos | 723 | 89.2 (645) | 10.8 (78) | 0 (0) | 0.054 | |
Dean et al.b (17) | High-risk, USA | Mixed | Neg | 883 | 81.9 (724) | 15.6 (138) | 2.4 (21) | 0.10 |
High-risk, USA | Mixed | Pos | 1883 | 85.9 (1618) | 14.0 (264) | 0.0005 (1) | 0.071 | |
High-risk, USA | African-Amer | Mixed | 620 | 96.6 (599) | 3.4 (21) | 0 (0) | 0.017 | |
High-risk, USA | Caucasian | Mixed | 1250 | 0.115 | ||||
Low-risk, USA | Caucasian | Mixed | 143 | 0.080 | ||||
Huang et al. (12) | High-risk, USA | Caucasian | Pos | 461 | 79.8 (368) | 20.2 (93) | 0 (0) | 0.101 |
High-risk, USA | Caucasian | Neg | 446 | 78.0 (348) | 16.7 (82) | 3.6 | 0.128 | |
Blood donors, USA | Caucasian (95%) | Neg | 637 | 85.2 | 13.3 | 1.4 | 0.08 | |
General, Africa/Haiti | Black | Mixed | 137 | 100 | 0 (0) | 0 (0) | 0 | |
General, Asia | China/Thai/other | Mixed | 191 | 100 | 0 (0) | 0 (0) | 0 | |
Michael et al. (18) | High-risk, USA | Mixed | Pos | 406 | 87.5 (348) | 14.3 (58) | 0 (0) | 0.071 |
High-risk, USA | Mixed | Neg | 21 | 71.4 (15) | 9.5 (2) | 19.1 (4) | 0.238 | |
Intermediate-risk, USA | Mixed | Neg | 240 | 78.3 (188) | 20.4 (49) | 1.3 (3) | 0.115 | |
Biti et al. (20) | High-risk, Australia | Caucasian | Pos | 265 | N/Ac | N/A | 0.004 (1) | N/A |
Theodoru et al. (22) | High-risk, Europe | Pos | 412 | N/A | N/A | 0.002 (1) | N/A | |
Eugenolsen et al. (23) | High-risk, Denmark | Caucasian | Neg | 35 | 74 (26) | 20 (7) | 6 (2) | 0.157 |
High-risk, Denmark | Caucasian | Pos | 99 | 78 (77) | 22 (22) | 0 | 0.111 | |
Blood donors, Denmark | Caucasian | Neg | 37 | 73 (27) | 24 (9) | 3 (1) | 0.149 | |
Zimmerman et al. (19) | Blood donors, North America | Caucasian | Neg | 387 | 77.5 (300) | 21.7 (84) | 0.8 (3) | 0.116 |
African Amer | Neg | 294 | 94.2 (277) | 5.8 (17) | 0 (0) | 0.29 | ||
Hispanic | Neg | 290 | 92.8 (269) | 6.9 (20) | 0.3 (1) | 0.38 | ||
Asian | Neg | 164 | 99.4 (163) | 0.6 (1) | 0 (0) | 0.003 | ||
Native Amer. | Neg | 87 | 83.9 (73) | 12.6 (11) | 3.4 (3) | 0.098 | ||
Blood donors, India | Tamil | Neg | 46 | 100 (46) | 0 (0) | 0(0) | 0 | |
Blood donors, W. Africa | Black | Neg | 40 | 100 (40) | 0 (0) | 0 (0) | 0 | |
High Risk, USA | Caucasian | Pos | 614 | 77.4 (475) | 22.6 (139) | 0 (0) | 0.113 | |
High Risk, USA | African Amer | Pos | 86 | 97.7 (84) | 2.3 (2) | 0 (0) | 0.012 | |
High Risk, USA | Hispanic | Pos | 45 | 93.3 (42) | 6.7 (3) | 0 (0) | 0.033 | |
High Risk USA | Caucasian | Neg | 111 | 73.9 (82) | 21.6 (24) | 4.5 (5) | 0.0153 | |
High Risk, USA | African Amer | Neg | 2 | 50.0 (1) | 0 (0) | 0.250 | ||
High Risk, USA | Hispanic | Neg | 12 | 91.7 (11) | 8.3 (1) | 0 (0) | 0.042 |
a CCR5 genotypes: W/W, homozygous wild type; W/∆ 32, heterozygous wild type/32bp deletion; ∆32/∆32, homozygous for the 32 bp deletion.
b Numbers updated to include additional Multicenter Hemophiulia Cohort Study patients studied by O'Brien et al. (21) and Dean et al. (pers .comm.).
cNotSUP>cNot available
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.