title: Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway.
abstract: Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University, Wuhan 430072, China.
authors.forename: Caoqi
authors.initials: C
authors.lastname: Lei
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University, Wuhan 430072, China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Huanan
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University, Wuhan 430072, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University, Wuhan 430072, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
authors.forename: Haixue
authors.initials: H
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011971:Receptors, Immunologic; D015398:Signal Transduction; D034421:Sus scrofa; D017361:Viral Nonstructural Proteins / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1