Concordance of CCR5 Genotypes that Influence Cell-Mediated Immunity and HIV-1 Disease Progression Rates

Catano, G. and Chykarenko, Z.A. and Mangano, A. and Anaya, J-M and He, W. and Smith, A. and Bologna, R. and Sen, L. and Clark, R.A. and Lloyd, A. and Shostakovich-Koretskaya, L. and Ahuja, S.K. (2011) Concordance of CCR5 Genotypes that Influence Cell-Mediated Immunity and HIV-1 Disease Progression Rates. Journal of Infectious Diseases (№ 203). pp. 263-272.

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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-D32-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-D32 heterozygosity partly reflect the effect of the nonn32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayedtype 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.

Item Type: Article
Subjects: Infectious diseases
HIV infection
Divisions: Departments > Department of Infectious Diseases
Depositing User: Анастасия Жигар
Date Deposited: 20 Feb 2014 01:02
Last Modified: 13 Feb 2015 14:58

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