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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.
- Source :
-
Journal of Virology . May2014, Vol. 88 Issue 9, p4866-4876. 11p. - Publication Year :
- 2014
-
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. MERS-CoV 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 RNA-binding 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MERS coronavirus
*CORONAVIRUSES
*DOUBLE-stranded RNA
*VIRUSES
*HERPESVIRUS diseases
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 88
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 95900108
- Full Text :
- https://doi.org/10.1128/JVI.03649-13