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Journal of Virology, November 1998, p. 9257-9266, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Adenovirus Induction of an Interferon-Regulatory Factor during Entry into the Late Phase of Infection

David Feigenblum,dagger Robert Walker, and Robert J. Schneider*

Department of Biochemistry and Microbiology, Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016

Received 11 May 1998/Accepted 17 July 1998

Virus infection of animal cells can induce intracellular antiviral responses mediated by the induction of interferon-regulatory transcription factors (IRFs), which bind to and control genes directed by the interferon-stimulated response element (ISRE). The purpose of this study was to determine whether adenovirus (Ad) induces IRFs during infection, because they might play a role in promoting viral pathogenesis. Here we show that after the late phase of infection, Ad induces a transcription factor related to the IRF family of factors. The IRF is induced shortly after Ad entry into late phase and is shown to stimulate ISRE-directed transcription, to require activation by protein tyrosine kinase signalling, and to be induced several hours prior to the inhibition of cell protein synthesis. Inhibition of tyrosine kinase activity blocks Ad induction and activation of the IRF. Attempts to identify the Ad-induced factor immunologically and by photo-UV cross-linking indicate that it is likely a novel member of the IRF family. Finally, several independent lines of evidence also suggest that Ad induction of the IRF might correlate with the ability of the virus to block host cell protein synthesis later during infection.

* Corresponding author. Mailing address: Department of Biochemistry and Microbiology, Kaplan Cancer Center, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-6006. Fax: (212) 263-8166. E-mail: schner01{at}mcrcr6.med.nyu.edu.

dagger Present address: Department of Medicine, New York University School of Medicine, New York, NY 10016.

Journal of Virology, November 1998, p. 9257-9266, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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