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Antiviral Res. 2019 Jan;161:70-84. doi: 10.1016/j.antiviral.2018.10.010. Epub 2018 Oct 10.

Encephalomyocarditis virus 2C protein antagonizes interferon-β signaling pathway through interaction with MDA5.

Author information

1
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
2
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China. Electronic address: baijuan@njau.edu.cn.

Abstract

Encephalomyocarditis virus (EMCV) is one of the most important picornavirus. It infects many mammalian species and causes encephalitis, myocarditis, neurologic diseases, diabetes and reproductive disorders in pigs. And it evolves mechanisms for escaping innate immune responses. But the viral pathogenesis has not been understood completely. In this study, we firstly found that EMCV protein 2C is a strong IFN-β antagonist that interacts with MDA5 to inhibit induction of the IFN-β signal pathway. The mutations in amino acid residue V26 of 2C decrease the inhibition of IFN-β promoter activity and lost the ability to interact with MDA5, compared with wild type 2C protein. The rescued viruses with mutations in 2C (rV26A and rK25-3A) induced significantly higher IFN-β mRNA and protein levels in PK-15, HEK-293A and N2a cells, compared to wild type EMCV and the repaired viruses rV26A(R) and rK25-3A(R). These data indicate that the amino acid residue V26 of EMCV 2C plays important roles in inhibiting type I IFN production by interacting with MDA5.

KEYWORDS:

EMCV; IFN-β inhibition; MDA5; Non-structural protein 2C

PMID:
30312637
DOI:
10.1016/j.antiviral.2018.10.010
[Indexed for MEDLINE]

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