Introduction: Interferon regulatory factor-7 (IRF-7), the “master regulator” of type 1 interferon, has shown to orchestrate anti-viral immune responses via fine-tuning expression of interferons and interferon-stimulated genes. Methods: IRF-7 levels were examined using multi-parametric flow-cytometry in HIV-uninfected Manitoban donors and in HIV-infected and HIV-uninfected Kenyan volunteers from a well-characterized Kenyan sex worker cohort. IRF-7 expression level was reduced by IRF-7 specific siRNA or shRNA encoded in lentivirus and administered into ex-vivo CD4+ T cells by transfection or transduction. Results: In unstimulated PBMC, IRF-7 was constitutively expressed at low levels in every defined subset we examined. We observed less HIV-infected cells (~10%) with IRF-7 knockdown, suggesting that IRF-7 may play a role in HIV infection. Conclusions: Unexpectedly, it was found that even though IRF-7 had been implicated in orchestrating antiviral events, reducing IRF-7 expression in ex vivo CD4+ T cells did not increase the cellular susceptibility to productive HIV infection. / February 2017