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Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-? production via blocking IPS-1 and RIG-I.

ABSTRACT: Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly emerging enteric coronavirus, is considered to be associated with swine acute diarrhea syndrome (SADS) which has caused significantly economic losses to the porcine industry. Interactions between SADS-CoV and the host innate immune response is unclear yet. In this study, we used IPEC-J2 cells as a model to explore potential evasion strategies employed by SADS-CoV. Our results showed that SADS-CoV infection failed to induce IFN-? production, and inhibited poly (I:C) and Sendai virus (SeV)-triggered IFN-? expression. SADS-CoV also blocked poly (I:C)-induced phosphorylation and nuclear translocation of IRF-3 and NF-?B. Furthermore, SADS-CoV did not interfere with the activity of IFN-? promoter stimulated by IRF3, TBK1 and IKK?, but counteracted its activation induced by IPS-1 and RIG-I. Collectively, this study is the first investigation that shows interactions between SADS-CoV and the host innate immunity, which provides information of the molecular mechanisms underlying SASD-CoV infection.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7114844 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I.

Zhou Zhihai Z Sun Yuan Y Yan Xiaoling X Tang Xiaoyu X Li Qianniu Q Tan Yaorong Y Lan Tian T Ma Jingyun J

Virus research 20191226

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly emerging enteric coronavirus, is considered to be associated with swine acute diarrhea syndrome (SADS) which has caused significantly economic losses to the porcine industry. Interactions between SADS-CoV and the host innate immune response is unclear yet. In this study, we used IPEC-J2 cells as a model to explore potential evasion strategies employed by SADS-CoV. Our results showed that SADS-CoV infection failed to induce IFN-β produ ...[more]

PMID: 31884203

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Project description:UnlabelledPorcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea in piglets and results in large economic losses in many Asian and European countries. A large-scale outbreak of porcine epidemic diarrhea occurred in China in 2010, and the virus emerged in the United States in 2013 and spread rapidly, posing significant economic and public health concerns. Previous studies have shown that PEDV infection inhibits the synthesis of type I interferon (IFN), and viral papain-like protease 2 has been identified as an IFN antagonist. In this study, we found that the PEDV-encoded nucleocapsid (N) protein also inhibits Sendai virus-induced IFN-β production, IFN-stimulated gene expression, and activation of the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB. We also found that N protein significantly impedes the activation of the IFN-β promoter stimulated by TBK1 or its upstream molecules (RIG-I, MDA5, IPS-1, and TRAF3) but does not counteract its activation by IRF3. A detailed analysis revealed that the PEDV N protein targets TBK1 by direct interaction and that this binding sequesters the association between TBK1 and IRF3, which in turn inhibits both IRF3 activation and type I IFN production. Together, our findings demonstrate a new mechanism evolved by PEDV to circumvent the host's antiviral immunity.ImportancePEDV has received increasing attention since the emergence of a PEDV variant in China and the United States. Here, we identify nucleocapsid (N) protein as a novel PEDV-encoded interferon (IFN) antagonist and demonstrate that N protein antagonizes IFN production by sequestering the interaction between IRF3 and TBK1, a critical step in type I IFN signaling. This adds another layer of complexity to the immune evasion strategies evolved by this economically important viral pathogen. An understanding of its immune evasion mechanism may direct us to novel therapeutic targets and more effective vaccines against PEDV infection.

Dataset Information

Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-? production via blocking IPS-1 and RIG-I.

Publications

Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I.

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