title: Porcine reproductive and respiratory syndrome virus 3C protease cleaves the mitochondrial antiviral signalling complex to antagonize IFN-β expression.
abstract: Porcine reproductive and respiratory syndrome, a highly infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), has developed various strategies to evade the host innate immune response, including the suppression of type I IFN activation. The mitochondrial antiviral signalling protein (MAVS) is an important bridging adaptor of retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 signalling pathways. Here, we demonstrated that the 3C-like protease (3CLSP) of PRRSV prevented the induction of IFN-β by cleaving MAVS in a proteasome- and caspase-independent manner. Moreover, this cleavage ability was dependent on the protease activity of 3CLSP. Mutations specifically disrupting the cysteine protease activity of 3CLSP eliminated MAVS cleavage and the inhibition of IFN induction. Subsequently, we determined that 3CLSP cleaved MAVS at Glu268. Remarkably, a MAVS point mutation at Glu268 rendered MAVS resistant to 3CLSP cleavage. These results reveal a novel PRRSV mechanism to escape host immunity by directly cleaving MAVS.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Shangen
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Dang
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.|Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Animal Infections, College of Veterinary Medicine, Wuhan 430070, Hubei, PR China.|State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000086042:3C Viral Proteases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D020169:Caspases / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006868:Hydrolysis; D057131:Immune Evasion; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D024101:Mitochondrial Proteins; D014764:Viral Proteins; D016899:Interferon-beta; D020169:Caspases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D046988:Proteasome Endopeptidase Complex