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The effect of genetic variation in chemokines and their receptorson HIV transmission and progression to AIDS
Author(s) -
O'Brien Stephen J.,
Moore John P.
Publication year - 2000
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2000.17710.x
Subject(s) - chemokine receptor , biology , ccr2 , chemokine , receptor , population , cxcr4 , allele , immunology , chemokine receptor ccr5 , ccr3 , genetics , gene , virus , medicine , environmental health
The pivotal discovery that two chemokine receptors, CCR5 and CXCR4, serve along with the T-cell receptor-interacting CD4 molecule as the principal co-receptors for HIV-1 entry stimulated a search for common genetic polymorphism in their genes which might affect the course of AIDS. Four mutational variants, CCR5-delta32, CCR5-P1, CCR2-641 and SDF1-3'A were discovered to play a regulatory role in HIV-1 infection, in the rate of progression to AIDS or both. Plausible physiological mechanisms to explain the population genetic association by these alleles have been advanced and are discussed critically here. Genetic ablation of AIDS progression by chemokine receptor and ligand gene variants has catalyzed development of novel therapies targeting the virus-co-receptor interaction. The functional and therapeutic implications of these AIDS restriction genes for disease progression and intervention are explored in this review.