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Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates
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Catano G.
Chykarenko Z.A.
Mangano A.
Anaya, Juan-Manuel
He W.
Smith A.
Bologna R.
Sen L.
Clark R.A.
Lloyd A.
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2011
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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-D32 allele, when paired with non-?32-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-?32 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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
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Chemokine receptor CCR5 , Genetic , Delayed , Cellular , CCR5 , Virus receptor , Acquired immune deficiency syndrome , Adult , AIDS patient , Allele , Article , Cellular immunity , Cohort analysis , Controlled study , Delayed hypersensitivity , Disease course , Female , Gene expression , Genetic association , Genetic transcription , Genotype , Haplotype , Heterozygosity , Human , Human immunodeficiency virus 1 , Human immunodeficiency virus 1 infection , Human immunodeficiency virus infected patient , Immunoregulation , In vivo study , Major clinical study , Male , Nucleotide sequence , Phenotype , Priority journal , Single nucleotide polymorphism , Virus immunity , Virus pathogenesis , Virus replication , Adult , Disease Progression , Female , Genotype , Haplotypes , HIV Infections , HIV-1 , Humans , Hypersensitivity , Immunity , Male , Polymorphism , Receptors
