TY - JOUR
T1 - Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates
AU - Catano, Gabriel
AU - Chykarenko, Zoya A.
AU - Mangano, Andrea
AU - Anaya, J. M.
AU - He, Weijing
AU - Smith, Alison
AU - Bologna, Rosa
AU - Sen, Luisa
AU - Clark, Robert A.
AU - Lloyd, Andrew
AU - Shostakovich-Koretskaya, Ludmila
AU - Ahuja, Sunil K.
N1 - Funding Information:
This work was supported by the US Civilian Research and Development Foundation (UKB1-2931-DN-08 to L.S.-K.), the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and the National Institutes of Health (R37-AI046326 and R01-AI043279 to S.K.A.). S.K.A. is also supported by a VA MERIT award and is a recipient of the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1/15
Y1 - 2011/1/15
N2 - 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-D32 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-Δ32 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.
AB - 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-D32 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-Δ32 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.
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U2 - 10.1093/infdis/jiq023
DO - 10.1093/infdis/jiq023
M3 - Article
C2 - 21288827
AN - SCOPUS:79851475866
SN - 0022-1899
VL - 203
SP - 263
EP - 272
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -
