Abstract |
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.
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Authors | Hezhao Ji, Terry Blake Ball, Zhujun Ao, Joshua Kimani, Xiaojian Yao, Francis Allan Plummer |
Journal | Scandinavian journal of infectious diseases
(Scand J Infect Dis)
Vol. 42
Issue 5
Pg. 389-94
(May 2010)
ISSN: 1651-1980 [Electronic] England |
PMID | 20100115
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interferon Regulatory Factor-1
- Luciferases
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Topics |
- Blotting, Western
- Cells, Cultured
- Female
- Genes, Reporter
- Genotype
- HIV Long Terminal Repeat
(genetics)
- HIV-1
(growth & development)
- Humans
- Immunity, Innate
- Interferon Regulatory Factor-1
(biosynthesis, genetics)
- Kenya
- Leukocytes, Mononuclear
(virology)
- Luciferases
(biosynthesis, genetics)
- Polymorphism, Genetic
- Transcription, Genetic
- Vesiculovirus
(genetics)
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