Open AccessISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response
Author(s) -
Ying Li,
Chao Li,
Peng Xue,
Bo Zhong,
Aiping Mao,
Yong Ran,
He Chen,
YanYi Wang,
Fuquan Yang,
HongBing Shu
Publication year - 2009
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0900818106
Subject(s) - vesicular stomatitis virus , biology , gene knockdown , sendai virus , virus , viral replication , microbiology and biotechnology , irf3 , signal transduction , mediator , virology , gene , transcription factor , genetics
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.
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