Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response

Kam Leung Siu, Man Lung Yeung, Kin Hang Kok, Kit San Yuen, Chun Kew, Pak Yin Lui, Chi Ping Chan, Herman Tse, Patrick C.Y. Woo, Kwok Yung Yuen, Dong Yan Jin

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168 Citations (Scopus)

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I·C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I·C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERSCoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNAbinding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity.

Original languageEnglish
Pages (from-to)4866-4876
Number of pages11
JournalJournal of Virology
Volume88
Issue number9
DOIs
Publication statusPublished - May 2014
Externally publishedYes

ASJC Scopus Subject Areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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