Repression of interferon regulatory factor 3 by the Epstein-Barr virus immediate-early protein Rta is mediated through E2F1 in HeLa cells.

Interferon regulatory factor 3 (IRF-3), an essential transcriptional regulator of the interferon (IFN) genes, is important in the host defense against viral and microbial infection. Epstein-Barr virus (EBV) immediate-early protein replication and transcription activator (Rta) and the transcription factor E2F1 are two important inhibitive factors, which repress IRF-3 expression. Numerous studies have identified that Rta can directly bind to the Rta-response element in promoters of its target genes and regulate their expression. In the present study, we demonstrated that Rta represses the expression of IRF-3 by E2F1 rather than through its traditional way. Transient transfection analysis and chromatin immunoprecipitation (ChIP) assays revealed that the overexpression of Rta elevated the expression of E2F1 and increased the binding of E2F1 to the promoter of IRF-3. The mutation of the E2F1‑binding site and the knocking down of E2F1 by small interfering RNA (siRNA) can eradicate the inhibitory effect of Rta. These results suggested that Rta represses IRF-3 expression by increasing E2F1 binding to the IRF-3 promoter.