Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response.
Viral infection causes activation of transcription factors NF-kappaB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. Here we show that knockdown of the E3 ubiquitin ligases cIAP1 and cIAP2 markedly inhibited virus-triggered activation of IRF3 and NF-kappaB as well as IFN-beta induction. Knockdown of cIAP1 and cIAP2 also inhibited cytoplasmic dsRNA-triggered cellular antiviral response. Endogenous coimmunoprecipitation experiments indicated that viral infection caused recruitment of cIAP1 and cIAP2 to TRAF3, TRAF6, and VISA. Furthermore, we demonstrated that cIAP1- and cIAP2-mediated virus-triggered ubiquitination of TRAF3 and TRAF6. These findings suggest that virus-triggered ubiquitination of TRAF3 and TRAF6 by cIAP1 and cIAP2 is essential for type I IFN induction and cellular antiviral response.
Mao
Ai-Ping
AP
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Li
Shu
S
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Zhong
Bo
B
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Li
Ying
Y
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Yan
Jie
J
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Li
Qi
Q
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Teng
Chengwen
C
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Shu
Hong-Bing
HB
College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: shuh@whu.edu.cn.
D000998:Antiviral Agents / Q000494:pharmacology*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000998:Antiviral Agents; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D048008:TNF Receptor-Associated Factor 3; D048029:TNF Receptor-Associated Factor 6; D016899:Interferon-beta; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases