ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response.
IFN-stimulated gene 56 (ISG56) is one of the first identified proteins induced by viruses and type I IFNs. In this study, we identified ISG56 as a virus-induced protein associated with MITA, an adapter protein involved in virus-triggered induction of type I IFNs. Overexpression of ISG56 inhibited Sendai virus-triggered activation of IRF3, NF-kappaB, and the IFN-beta promoter, whereas knockdown of ISG56 had opposite effects. Consistently, overexpression of ISG56 reversed cytoplasmic poly(I:C)-induced inhibition of vesicular stomatitis virus (VSV) replication, whereas knockdown of ISG56 inhibited VSV replication. Competitive coimmunoprecipitation experiments indicated that ISG56 disrupted the interactions between MITA and VISA or TBK1, two components in the virus-triggered IFN signaling pathways. These results suggest that ISG56 is a mediator of negative-feedback regulation of virus-triggered induction of type I IFNs and cellular antiviral responses.
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Ying
Y
Li
Chao
C
Li
Peng
P
Xue
Bo
B
Zhong
Ai-Ping
AP
Mao
Yong
Y
Ran
He
H
Chen
Yan-Yi
YY
Wang
Fuquan
F
Yang
Hong-Bing
HB
Shu
D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D018353:Rhabdoviridae Infections / Q000378:metabolism; D029082:Sendai virus / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; C484290:IFIT1 protein, human; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016899:Interferon-beta