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Mol Cell Biol, July 1998, p. 3796-3802, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cytomegalovirus Activates Interferon Immediate-Early Response Gene Expression and an Interferon Regulatory Factor 3-Containing Interferon-Stimulated Response Element-Binding Complex

Lorena Navarro,1 Kerri Mowen,1 Steven Rodems,1 Brian Weaver,2 Nancy Reich,2 Deborah Spector,1 and Michael David1 *

Department of Biology, University of California at San Diego, La Jolla, California 92093,1 and Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York 117942

Received 25 November 1997/Returned for modification 29 December 1997/Accepted 12 March 1998

Interferon establishes an antiviral state in numerous cell types through the induction of a set of immediate-early response genes. Activation of these genes is mediated by phosphorylation of latent transcription factors of the STAT family. We found that infection of primary foreskin fibroblasts with human cytomegalovirus (HCMV) causes selective transcriptional 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 synthesis but is prevented by protein tyrosine kinase inhibitors. Further analysis revealed that HCMV infection induced the DNA binding of a novel complex, tentatively called cytomegalovirus-induced interferon-stimulated response element binding factor (CIF). CIF is composed, at least in part, of the recently identified interferon regulatory factor 3 (IRF3), but it does not contain the STAT1 and STAT2 proteins that participate in the formation of interferon-stimulated gene factor 3. IRF3, which 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 interferon-stimulated genes without the need for prior synthesis of interferons might provide the host cell with a potential shortcut in the activation of its antiviral defense.

* Corresponding author. Mailing address: University of California, San Diego, Department of Biology, Bonner Hall 3138, 9500 Gilman Dr., La Jolla, CA 92093-0322. Phone: (619) 822-1108. Fax: (619) 822-1106. E-mail: midavid{at}ucsd.edu.

Mol Cell Biol, July 1998, p. 3796-3802, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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