Adenovirus induction of an interferon-regulatory factor during entry into the late phase of infection.
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.
Department of Biochemistry and Microbiology, Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
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Feigenblum
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Walker
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Schneider
D000256:Adenoviridae / Q000472:pathogenicity*; D000257:Adenoviridae Infections / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D039561:Eukaryotic Initiation Factor-4E; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D039561:Eukaryotic Initiation Factor-4E; D015345:Oligonucleotide Probes; D010448:Peptide Initiation Factors; D015534:Trans-Activators; D004247:DNA; D007372:Interferons; D011505:Protein-Tyrosine Kinases