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Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.

ABSTRACT: Viral infection leads to activation of the transcription factors interferon regulatory factor-3 and NF-kappaB, 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-beta induction. Overexpression of DAK also inhibited cytoplasmic dsRNA and SeV-induced activation of the IFN-beta promoter, whereas knockdown of endogenous DAK by RNAi activated the IFN-beta promoter, and increased cytoplasmic dsRNA- or SeV-triggered activation of the IFN-beta 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.

SUBMITTER: Diao F 

PROVIDER: S-EPMC1913852 | biostudies-other | 2007 Jul

REPOSITORIES: biostudies-other

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Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.

Diao Feici F   Li Shu S   Tian Yang Y   Zhang Min M   Xu Liang-Guo LG   Zhang Yan Y   Wang Rui-Peng RP   Chen Danying D   Zhai Zhonghe Z   Zhong Bo B   Tien Po P   Shu Hong-Bing HB  

Proceedings of the National Academy of Sciences of the United States of America 20070628 28

Viral infection leads to activation of the transcription factors interferon regulatory factor-3 and NF-kappaB, 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  ...[more]