ROLE OF CHEMOKINE RECEPTOR IN AIDS Despite repeated exposure to the AIDS virus, some individuals do not exhibit AIDS. Alkhtib et al, 1996, Dean et al, 1996, Deng et al, 1996, Dragic et al, 1996, Feng et al, 1996, Liu et al, 1996, Sampson et al, 1996 have identified a molecular basis for this resistance. Deng et al, (1996) and Dragic et al (1996) identified the C-C chemokine receptor, CMKBR5, as a co-receptor for the human immunodeficiency virus-1 (HIV-1). It seems that both the CMKBR5 and fusin (Feng et al, 1996) contribute to the fusion of HIV-1 with the CD4(+) in the plasma membrane of cells. Based on its similarlity to murine C-C chemokine, the human C-C chemokine receptor gene was isolated from a human genomic DNA library (Sampson et al, 1996). The human gene, which they designated ChemR13, encodes a 352-amino acid protein with a prdicted molecular mass of 40,600 kDa and a potential N-linked glycosylation site. This chemokine receptor serves as a secondary receptor fon the CD4 positive cells for certain strains of HIV-1. Dragic et al, 1996 showed that the beta-chemokines MIP-1alpha, MIP-1beta and RANTES inhibit infection of CD4+ T cells by primary, non-syncytium-inducing (NSI) HIV-1 strains at the virus entry stage, and also block env-mediated cell-cell membrane fusion. Dean et al, 1996 by examination of 1955 patients showed, that among these, the 612 individuals who were exposed to the HIV-1 and remained HIV-1 antibody negative, harbored a deletion of the chemokine receptor 5. This deletion was found at a significantly higher rate in groups of individuals who survived the infection for more than 10 years. Therefore, it was concluded that the deletion in the chemokine receptor may delay the progression of AIDS in patients with HIV infection. REFERENCES Alkhatib, G.; Combadiere, C.; Broder, C. C.; Feng, Y.; Kennedy, P. E.; Murphy, P. M.; Berger, E. A. : CC CKR5: a RANTES, MIP-1-alpha, MIP-1-beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272: 1955-1958, 1996. Dean, M.; Carrington, M.; Winkler, C.; Huttley, G. A.; et al. : Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273: 1856-1861, 1996. Deng, H.; Liu, R.; Ellmeier, W.; Choe, S.; Unutmaz, D.; Burkhart, M.; Di Marzio, P.; Marmon, S.; Sutton, R. E.; Hill, C. M.; Davis, C. B.; Peiper, S. C.; Schall, T. J.; Littman, D. R.; Landau, N. R. : Identification of a major co-receptor for primary isolates of HIV-1. Nature 381: 661-666, 1996. MEDLINE UID : 96260017 Dragic, T.; Litwin, V.; Allaway, G. P.; Martin, S. R.; Huang, Y.; Nagashima, K. A.; Cayanan, C.; Maddon, P. J.; Koup, R. A.; Moore, J. P.; Paxton, W. A. : HIV-1 entry into CD4(+) cells is mediated by the chemokine receptor CC-CKR-5. Nature 381: 667-673, 1996. MEDLINE UID : 96260018 Feng, Y.; Broder, C. C.; Kennedy, P. E.; Berger, E. A. : HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272: 872-876, 1996. Liu, R.; Paxton, W. A.; Choe, S.; Ceradini, D.; Martin, S. R.; Horuk, R.; MacDonald, M. E.; Stuhlmann, H.; Koup, R. A.; Landau, N. R. : Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86: 367-377, 1996. Samson, M.; Labbe, O.; Mollereau, C.; Vassart, G.; Parmentier, M. : Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35: 3362-3367, 1996. MEDLINE UID : 96241590 Samson, M.; Libert, F.; Doranz, B. J.; Rucker, J.; Liesnard, C.; Farber, C.-M.; Saragosti, S.; Lapoumeroulie, C.; Cogniaux, J.; Forceille, C.; Muyldermans, G.; Verhofstede, C.; Burtonboy, G.; Georges, M.; Imai, T.; Rana, S.; Yi, Y.; Smyth, R. J.; Collman, R. G.; Dom, R. W.; Vassart, G.; Parmentier, M. : Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382: 722-725, 1996. RESOURCES HIV Genetic Sequences Database Glossary of AIDS Terms Medical Terms AIDS Magazines, Periodical and Libraries Search CSULA Library (login as library) LITDB Database Using DBGET(Literature Database) AIDS Bibliography LISTSERVE Subscription AIDS Research at BITMED UNCOVER at CSULA NAIC AIDS DATA: A User Guide All Service Listing Commonly Asked Questions and Answers WHO; Information on Epidemiology Global Programme on AIDS (WHO) American Anthropological Association's Commission on AIDS research and education (Tulane University) Biology of AIDS Course Syllabus The AIDS Quilt page HIV Gene Sequencing AIDS: A National Epidemic. Data on US AIDS Rates. AIDS resources: A list from QRD (Queer Resources Directory) Cross-Species Transplant Global Programme on AIDS: "The Current Situation of the HIV/AIDS Pandemic" Women and AIDS: Gender for Action IX International Conference on AIDS in Kampala, 1995 Database Links: Gene Map Locus: 3p21