IRF-1 is required for full NF-κB transcriptional activity at the human immunodeficiency virus type 1 long terminal repeat enhancer

Human immunodeficiency virus type 1 (HIV-1) gene expression is controlled by a complex interplay between viral and host factors. We have previously shown that interferon-regulatoty factor 1 (IRX-1) is stimulated early after HIV-1 infection and regulates promoter transcriptional activity even in the absence of the viral transactivator Tat. In this work we demonstrate that IRF-1 is also required for full NF-kappa B transcriptional activity. We provide evidence that IRF-1 and NF-kappa B form a functional complex at the long terminal repeat (LTR) kappa B sites, which is abolished by specific mutations in the two adjacent kappa B sites in the enhancer region. Silencing IRF-1 with small interfering RNA resulted in impaired NF-kappa B-mediated transcriptional activity and in repressed HIV-1 transcription early in de novo-infected T cells. These data indicate that in early phases of HIV-1 infection or during virus reactivation from latency, when the viral transactivator is absent or present at very low levels, IRF-1 is an additional component of the p50/p65 heterodimer binding the LTR enhancer, absolutely required for efficient HIV-1 replication.