Polymorphisms in the IRF1 Gene Associated with Reduced HIV Susceptibility and Their Impact on Mrna Splicing and IRF1 Protein Expression

Background: Interferon regulatory factor 1 (IRF1) is induced by HIV early in the infection process and serves two functions: transactivation of the HIV-1 genome and thus replication, and eliciting antiviral innate immune responses. Previous work has shown association of three polymorphisms in IRF1, located at 619, the microsatellite and 6516 of the gene, with decreased susceptibility to HIV-1 infection and a reduced likelihood of seroconversion. Peripheral blood mononuclear cells from individuals with protective IRF1 genotypes exhibited significantly lower basal IRF1 expression and lower HIV-1 LTR transcription during initial stages of infection. DNA sequence variations can cause phenotypic changes by multiple mechanisms, including mRNA splicing and turnover. This study will further characterize the effect of identified polymorphisms on IRF1 expression and its effect on HIV-1.