ISG60 negatively regulates cell antiviral responses by disrupting the VISA-associated complexes
ISG60 negatively regulates cell antiviral responses by disrupting the VISA-associated complexes
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DOI：
10.1007/s11859-012-0795-6
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发表时间：
2012-03
影响因子：
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通讯作者：
Chao Li;Weiping Zhang;Y. Li;Lin Guo;H. Shu;Yu Liu
中科院分区：
文献类型：
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作者：
Chao Li;Weiping Zhang;Y. Li;Lin Guo;H. Shu;Yu Liu
病毒感染激活转录因子NF-κB和干扰素调节因子3（IRF 3），协同诱导I型干扰素（IFN），启动宿主先天性抗病毒应答。I型干扰素诱导的干扰素刺激基因56（ISG 56）是细胞抗病毒反应的负调节因子。在这项研究中，我们确定了ISG 60作为一个ISG 56相关蛋白的生化纯化和质谱分析。ISG 60的过表达抑制仙台病毒诱导的NF-κB和IRF 3的活化。免疫共沉淀试验表明ISG 60与MDA 5和VISA相互作用，这两种重要的信号蛋白参与病毒触发的I型IFN的产生。此外，ISG 60破坏了VISA与MDA 5或RIG-I的相互作用。这些结果表明ISG 60是病毒触发的I型IFN诱导的负调节剂。
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.