Negative Regulation of MDA5- but Not RIG-I-mediated Innate Antiviral Signaling by the Dihydroxyacetone Kinase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Jun 30

PMID 17600090

Citations 65

Authors

Feici Diao

Shu Li

Yang Tian

Min Zhang

Liang-Guo Xu

Yan Zhang

Rui-Peng Wang

Danying Chen

Zhonghe Zhai

Bo Zhong

Po Tien

Hong-Bing Shu

Affiliations

Soon will be listed here.

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.

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