Susceptibility to virus infection is determined by a Stat-mediated response to the autocrine effect of virus-induced type I interferon.
Interferon (IFN) signalling appears to be the predominant pathway that leads to the development of the host defence against virus. However, other mechanisms that are IFN independent may also be involved. The Stat1 transcription factor is specific for the IFN pathway and plays a central role in mediating many, if not all, IFN-dependent biological responses. Viral infection of cells in the presence or absence of Stat1 was studied to examine the role of IFN-dependent and independent antiviral mechanisms. A lower virus yield measured by plaque assays was observed following challenge with VSV, EMCV and NDV of cells in which either Stat1a or Stat1b was present compared to those lacking both forms of the Stat protein. The more efficient antiviral response was abolished when cells were infected with virus in the presence of IFN-neutralizing antibodies, suggesting that a Stat-dependent pathway is activated following virus infection by endogenously produced IFN. Virus-induced Stat protein translocation from the cytoplasmic compartment, detected within 3 h of infection, and Stat-dependent transcriptional activation of ISGF2 in response to virus challenge, were also abolished by neutralizing type I IFN. Thus, susceptibility to virus infection can be determined by the cell's ability to respond to autocrine IFN through the Stat-mediated pathway of gene induction.
Improta
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Duke University Medical Center, Durham NC 27710, USA.
Pine
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D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000276:immunology; D006801:Humans; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I / Q000096:biosynthesis*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D009500:Neutralization Tests; D009522:Newcastle disease virus / Q000276:immunology; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis; D015533:Transcriptional Activation; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014777:Virus Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; C494227:IRF9 protein, human; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma