title: Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO.
abstract: Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: wangdang511@126.com.
authors.forename: Dang
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Department of Biochemistry, Faculty of Agriculture, Benha University, Moshtohor, Toukh 13736, Egypt.
authors.forename: Mohamed Frahat
authors.initials: MF
authors.lastname: Foda
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: vet@mail.hzau.edu.cn.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
mesh_terms: D000818:Animals; D003332:Coronaviridae / Q000201:enzymology* / Q000235:genetics; D003333:Coronaviridae Infections / Q000201:enzymology / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013552:Swine; D013553:Swine Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D051550:I-kappa B Kinase; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases
keywords: 3C-like protease; Interferon-β; NEMO; Porcine deltacoronavirus; nsp5