Polymorphisms In Irf-1 Associated With Resistance To Hiv-1 Infection In Highly Exposed Uninfected Kenyan Sex Workers
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Date
2007-05Author
Ball, TB,
Ji, H
Kimani J, McLaren P, Marlin C, Hill AV, Plummer FA.
Kimani, J
McLaren, P
Marlin, C
Hill, AV
Plummer, FA.
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
OBJECTIVE:
To determine the correlation between polymorphisms in the IL-4 gene cluster and resistance to HIV-1 infection.
DESIGN:
: A cross-sectional genetic analysis of polymorphisms within the IL-4 gene cluster was conducted in a well-described female sex worker cohort from Nairobi, Kenya, known to exhibit differential susceptibility to HIV-1 infection.
METHODS:
Microsatellite genotyping was used to screen six microsatellite markers in the IL-4 gene cluster for associations with HIV-1 resistance. Further analysis of the interferon regulatory factor 1 (IRF-1) gene was conducted by genomic sequencing. Associations between IRF-1 gene polymorphisms and the HIV-1 resistance phenotype were determined using the chi-square test and Kaplan-Meier survival analysis. The functional consequence of IRF-1 polymorphism was conducted by quantitative Western blot.
RESULTS:
Three polymorphisms in IRF-1, located at 619, the microsatellite region and 6516 of the gene, showed associations with resistance to HIV-1 infection. The 619A, 179 at IRF-1 microsatellite and 6516G alleles were associated with the HIV-1-resistant phenotype and a reduced likelihood of seroconversion. Peripheral blood mononuclear cells from patients with protective IRF-1 genotypes exhibited significantly lower basal IRF-1 expression and reduced responsiveness to exogenous IFN-gamma stimulation.
CONCLUSION:
Polymorphisms in the IRF-1 gene are associated with resistance to infection by HIV-1 and a lowered level of IRF-1 protein expression. This study adds IRF-1, a transcriptional immunoregulatory gene, to the list of genetic correlates of altered susceptibility to HIV-1. This is the first report suggesting that a viral transcriptional regulator might contribute to resistance to HIV-1. Further functional analysis on the role of IRF-1 polymorphisms and HIV-1 resistance is underway
URI
http://hinari-gw.who.int/whalecomwww.ncbi.nlm.nih.gov/whalecom0/pubmed/17502719http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/41905
Citation
AIDS. 2007 May 31;21(9):1091-101Publisher
University of Nairobi Department of Medical Microbiology
Collections
- Faculty of Health Sciences (FHS) [10387]