Basal binding and recruitment of HDAC2 to IRF1 gene locus. (A) Basal HDAC2 binding at IRF1 promoter was assessed in the ex vivo PBMCs from HIV-S (▵, n = 10) and HIV-R (□, n = 11) individuals using ChIP-quantitative PCR with antibodies specific for HDAC2. Bars represent mean values. ***P < .0005. Not significant (P > .05). (B) HDAC2 recruitment to IRF1 promoter and intron7 after exogenous IFN-γ stimulation was examined at the indicated time points after IFN-γ stimulation. Quantitative PCR signals were normalized to input DNA. There was no difference in the levels of HDAC2 between the unstimulated samples cultured in media alone for 0, 60, or 180 minutes. Unstimulated sample from time = 0 is used as reference for calculating relative fold increases. (C) Study model: IRF1-responsive potential in HIV-R commercial sex workers and its implication in resistance to HIV acquisition. On stimulation by IFN-γ, IRF1 expression is robustly increased within 20 minutes at the transcriptional level. (i) Increased IRF1 binding to its target genes (eg, IL-12p35, IL-4) and the regulation of target gene express are also observed shortly after stimulation. (ii) Within an hour after stimulation, increases in IRF1 expression are controlled by the recruitment of HDAC2 to IRF1 loci and histone deacetylation spreading across the IRF1 gene. The transitory increase in IRF1 expression is sufficient in inducing comparable immune responses. (iii) At the same time, the rapid silencing of IRF1 expression may have a role in the HIV resistance by curtailing the transactivation of HIV-1 LTR during the early stages of viral infection and hence, allowing time for innate and acquired immunity of develop.