title: Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates.
abstract: We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity.
authors.affiliation: Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Catano
authors.forename: Zoya A
authors.initials: ZA
authors.lastname: Chykarenko
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.forename: J-M
authors.initials: JM
authors.lastname: Anaya
authors.forename: Weijing
authors.initials: W
authors.lastname: He
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
authors.forename: Ludmila
authors.initials: L
authors.lastname: Shostakovich-Koretskaya
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D006239:Haplotypes; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D008297:Male; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*
chemical_list: D019713:Receptors, CCR5