Reduced HIV-1 long terminal repeat transcription in subjects with protective interferon regulatory factor-1 genotype: A potential mechanism mediating resistance to infection by HIV-1
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Date
2010Author
Ji, Hezhao
Bal, Terry Blake
Ao, Zhujun
Kimani, Joshua
Yao, Xiaojian
Plummer, FA
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
We previously described the polymorphism in the interferon regulatory factor-1 (IRF-1) gene as a novel correlate of resistance to HIV-1 infection in a Kenyan female sex worker cohort. However, the underlying mechanisms likely mediating this association remained to be elucidated. The initiation of HIV-1 long terminal repeat (LTR) transcription in peripheral blood mononuclear cells (PBMCs) from subjects with different IRF-1 haplotypes, representing protective, intermediate and the least protective IRF-1 allele combinations, were investigated here. A single-cycle pseudovirus construct expressing vesicular stomatitis virus envelop G-protein (VSV-G) and having an HIV-1 pNL4.3 backbone with luciferase insert was used to infect PBMCs with different IRF-1 haplotypes. The efficiency of early HIV-1 LTR transcription was monitored using a luciferase assay. IRF-1 protein levels induced by the infection were measured by quantitative Western blot. Our results showed that PBMCs with the protective IRF-1 genotype demonstrated significantly lower HIV-1 LTR transcription during the initial stages of infection compared to PBMCs with other haplotypes, which correlated with the kinetics of IRF-1 responsiveness to HIV-1 infection in the cells. It suggests that IRF-1 genotypes alter the efficiency of early HIV-1 LTR transcription, likely via modulating expression of IRF-1. This may represent one mechanism mediating the association between IRF-1 polymorphisms and resistance to HIV-1 infection
URI
http://informahealthcare.com/doi/abs/10.3109/00365540903496536http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/51727
Citation
Scandinavian Journal of Infectious Diseases May 2010, Vol. 42, No. 5 , Pages 389-394Publisher
Department of Microbiology, University of Nairobi, Nairobi, Kenya National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, Manitoba, Canada Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada
Collections
- Faculty of Health Sciences (FHS) [10387]