title: Foot-and-mouth disease virus structural protein VP3 degrades Janus kinase 1 to inhibit IFN-γ signal transduction pathways.
abstract: Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV L(pro) and 3C(pro) on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN-γ-triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways.
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: b Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University , Wuhan , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Hua-Nan
authors.initials: HN
authors.lastname: Liu
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Zi-Xiang
authors.initials: ZX
authors.lastname: Zhu
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cao
authors.affiliation: b Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University , Wuhan , China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Xiang-Tao
authors.initials: XT
authors.lastname: Liu
authors.affiliation: a State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , China.
authors.forename: Hai-Xue
authors.initials: HX
authors.lastname: Zheng
authors.affiliation: b Collaborative Innovation Center for Viral Immunology, Medical Research Institute, Wuhan University , Wuhan , China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D003412:Cricetulus; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D059748:Proteolysis; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C442460:VP3 protein, Foot-and-mouth disease virus; D014443:Tyrosine; D007371:Interferon-gamma; D008156:Luciferases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Foot-and-mouth disease virus; IFN-γ; janus kinase 1; signaling pathway; structural protein VP3