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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.

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.
AuthorsHezhao Ji, Terry Blake Ball, Zhujun Ao, Joshua Kimani, Xiaojian Yao, Francis Allan Plummer
JournalScandinavian journal of infectious diseases (Scand J Infect Dis) Vol. 42 Issue 5 Pg. 389-94 (May 2010) ISSN: 1651-1980 [Electronic] England
PMID20100115 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Interferon Regulatory Factor-1
  • Luciferases
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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