CYTOMEGALOVIRUS ACTIVATES INTERFERON IMMEDIATE-EARLY RESPONSE GENE-EXPRESSION AND AN INTERFERON REGULATORY FACTOR 3-CONTAINING INTERFERON-STIMULATED RESPONSE ELEMENT-BINDING COMPLEX

Interferon establishes an antiviral state in numerous cell types throu gh the induction of a set of immediate-early response genes. Activatio n of these genes is mediated by phosphorylation of latent transcriptio n factors of the STAT family. We found that infection of primary fores kin fibroblasts with human cytomegalovirus (HCMV) causes selective tra nscriptional activation of the alpha/beta-interferon-responsive ISG54 gene. However, no activation or nuclear translocation of STAT proteins was detected. Activation of ISG54 occurs independent of protein synth esis but is prevented by protein tyrosine kinase inhibitors. Further a nalysis revealed that HCMV infection induced the DNA binding of a nove l complex, tentatively called cytomegalovirus-induced interferon-stimu lated response element binding factor (CIF). CIF is composed, at least in part, of the recently identified interferon regulatory factor 3 (I RF3), but it does not contain the STAT1 and STAT2 proteins that partic ipate in the formation of interferon-stimulated gene factor 3. IRF3, w hich has previously been shown to possess no intrinsic transcriptional activation potential, interacts with the transcriptional coactivator CREB binding protein, but not with p300, to form CIF, Activating inter feron-stimulated genes without the need for prior synthesis of interfe rons might provide the host cell with a potential shortcut in the acti vation of its antiviral defense.