ISG60 Negatively Regulates Cell Antiviral Responses by Disrupting the VISA-Associated Complexes

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Viral infection activates the transcription factors NF-κB and interferon regulatory factor 3 (IRF3),which collaborate to induce type Ⅰ interferons (IFNs) and initiate host innate antiviral response.IFN-stimulated gene 56 (ISG56) induced by type Ⅰ IFNs is a negative regulator of cellular antiviral response.In this study,we identified ISG60 as an ISG56-associated protein by biochemical purification and mass spectrometry analysis.Overexpression of ISG60 inhibited Sendai virus-induced activation of NF-κB and IRF3.Coimmunoprecipitation assays indicated that ISG60 interacted with MDA5 and VISA,two important signaling proteins participating in virus-triggered production of type Ⅰ IFNs.Furthermore,ISG60 disrupted the interaction of VISA with MDA5 or RIG-I.These results indicate that ISG60 is a negative regulator of virus-triggered type Ⅰ IFNs induction.
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