Loss of interferon alpha and interferon tau-induced antiviral protection in interferon regulatory factor-2 DNA-binding domain dominant negative mutants.
The role of the interferon regulatory factory (IRF) family of transcription factors in regulation of interferon alpha and interferon tau antiviral activity was investigated using a dominant negative mutant of IRF-2. The IRF-2 DNA binding domain (DBD), without the C-terminal regulatory region, was stably transfected into myeloid U937 cells. Expression of the IRF-2 DBD resulted in an increase in constitutive 2'5' oligoadenylate synthetase (OAS) levels, indicative of an active repressive mechanism, but was not sufficient to protect cells from challenge with vesicular stomatitis virus. Treatment of the DBD clones with interferons alpha A and tau failed to upregulate 2'5' OAS expression and did not elicit an antiviral response. While interferon alpha A was more sensitive than interferon tau to the inhibitory effects of the IRF-2 DBD, IRF-mediated gene induction is involved in successful interferon alpha and tau-induced anti-VSV activity.
Rubinstein
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YR
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park 20742, USA.
Pontzer
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CH
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D011257:Pregnancy Proteins / Q000378:metabolism / Q000494:pharmacology*; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D020298:U937 Cells; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000502:physiology
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I; D016898:Interferon-alpha; D011257:Pregnancy Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C020947:interferon tau; D015088:2',5'-Oligoadenylate Synthetase