Abstract
Swine acute diarrhea syndrome coronavirus (SADS-CoV), first discovered in 2017, is a porcine enteric coronavirus that can cause acute diarrhea syndrome (SADS) in piglets. Here, we studied the role of SADS-CoV nucleocapsid (N) protein in innate immunity. Our results showed that SADS-CoV N protein could inhibit type I interferon (IFN) production mediated by Sendai virus (Sev) and could block the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Simultaneously, the IFN-β promoter activity mediated by TANK binding kinase 1 (TBK1) or its upstream molecules in the RLRs signal pathway was inhibited by SADS-CoV N protein. Further investigations revealed that SADS-CoV N protein could counteract interaction between TNF receptor-associated factor 3 (TRAF3) and TBK1, which led to reduced TBK1 activation and IFN-β production. Our study is the first report of the interaction between SADS-CoV N protein and the host antiviral innate immune responses, and the mechanism utilized by SADS-CoV N protein provides a new insight of coronaviruses evading host antiviral innate immunity.
Highlights
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered porcine enteric coronavirus, causing acute diarrhea and vomiting, with a nearly 90% fatal mortality in piglets resulted in large economic losses for the pig-breeding industry in China [1,2,3,4,5]
The results showed no significant difference in mRNA expression of the Sendai virus (Sev) HN gene in transfected cells and in mock-transfected cells (Figure 1F), which indicated that the proliferation of Sev was not blocked by SADS-CoV N protein and further demonstrated the inhibition of N protein on IFN-b expression
The results showed that the overexpression of molecules in the RIG-I-like receptor (RLR)’ signaling pathway mentioned above all led to the significant increase of the activity of IFN-b promoter, but in cells co-transfected with the plasmid of pCMV-FLAG-N, the activity of IFN-b promoter induced by RIGI, Melanoma differentiation-associated gene 5 (MDA5), IPS-1, TNF receptor-associated factor 3 (TRAF3), inhibitor of kB kinase-ε (IKKε), and TANK binding kinase 1 (TBK1) was inhibited by SASDCoV N protein (Figures 3A–E)
Summary
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered porcine enteric coronavirus, causing acute diarrhea and vomiting, with a nearly 90% fatal mortality in piglets resulted in large economic losses for the pig-breeding industry in China [1,2,3,4,5]. The replicative intermediate such as nucleic acid produced by viruses in SADS-CoV N Protein Antagonizes Interferon-b infected cells that act as pathogen-associated molecular patterns (PAMPs) could be recognized by host pattern recognition receptors (PRRs) [6]. Retinoic acid-inducible gene I (RIG-I) and Melanoma differentiation-associated gene 5 (MDA5) are critical PRRs in the cytoplasm of host cells for recognizing viral dsRNA [7, 8]. After recognizing the cytoplasmic dsRNA, RIG-I and/or MDA5 is activated and interacts with the CARD region of interferon-beta (IFN-b) promoter stimulator through their caspase activation and recruitment domain region, stimulating the downstream TANK binding kinase 1 (TBK1) and inhibitor of kB kinase-ε (IKKε) [9, 10]. Activated TBK1 leads phosphorylation and nuclear translocation of IRF3 and NF-kB, which can induce type I interferon (IFN-I) production [11,12,13,14]
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