DHX29 functions as a RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity

Qingyuan Zhu, Peng Tan, Yinyin Li, Meng Lin, Chaoran Li, Jingrong Mao, Jun Cui, Wei Zhao, Helen Y. Wang, Rong Fu Wang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is a RNA helicase required for the translation of 5’ structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5’ structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity.

Original languageEnglish (US)
Article numbere1006886
JournalPLoS pathogens
Volume14
Issue number2
DOIs
StatePublished - Feb 2018

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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