Open AccessNegative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase
Author(s) -
Feici Diao,
Shu Li,
Yang Tian,
Min Zhang,
LiangGuo Xu,
Yan Zhang,
Ruipeng Wang,
Danying Chen,
Zhonghe Zhai,
Bo Zhong,
Po Tien,
HongBing Shu
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0700544104
Subject(s) - mda5 , biology , interferon , rna silencing , tlr3 , rig i , rna interference , gene knockdown , microbiology and biotechnology , innate immune system , rna , kinome , protein kinase r , signal transduction , virology , biochemistry , protein kinase c , gene , receptor , toll like receptor , mitogen activated protein kinase kinase
Viral infection leads to activation of the transcription factors interferon regulatory factor-3 and NF-κB, which collaborate to induce type I IFNs. The RNA helicase proteins RIG-I and MDA5 were recently identified as two cytoplasmic viral RNA sensors that recognize different species of viral RNAs produced during viral replication. In this study, we identified DAK, a functionally unknown dihydroacetone kinase, as a specific MDA5-interacting protein. DAK was associated with MDA5, but not RIG-I, under physiological conditions. Overexpression of DAK inhibited MDA5- but not RIG-I- or TLR3-mediated IFN-β induction. Overexpression of DAK also inhibited cytoplasmic dsRNA and SeV-induced activation of the IFN-β promoter, whereas knockdown of endogenous DAK by RNAi activated the IFN-β promoter, and increased cytoplasmic dsRNA- or SeV-triggered activation of the IFN-β promoter. In addition, overexpression of DAK inhibited MDA5- but not RIG-I-mediated antiviral activity, whereas DAK RNAi increased cytoplasmic dsRNA-triggered antiviral activity. These findings suggest that DAK is a physiological suppressor of MDA5 and specifically inhibits MDA5- but not RIG-I-mediated innate antiviral signaling.