title: Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING.
abstract: Feline panleucopenia virus (FPV) is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present study, we demonstrated that infection with the FPV strain Philips-Roxane failed to activate the interferon β (IFN-β) pathway but could antagonize the induction of IFN stimulated by Sendai virus (SeV) in F81 cells. Subsequently, by screening FPV nonstructural and structural proteins, we found that only nonstructural protein 2 (NS2) significantly suppressed IFN expression. We demonstrated that the inhibition of SeV-induced IFN-β production by FPV NS2 depended on the obstruction of the IFN regulatory factor 3 (IRF3) signaling pathway. Further, we verified that NS2 was able to target the serine/threonine-protein kinase TBK1 and prevent it from being recruited by stimulator of interferon genes (STING) protein, which disrupted the phosphorylation of the downstream protein IRF3. Finally, we identified that the C-terminus plus the coiled coil domain are the key domains of NS2 that are required for inhibiting the IFN pathway. Our study has yielded strong evidence for the FPV mechanisms that counteract the host innate immunity.
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. kang1989462@sina.com.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Kang
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. hattman324@163.com.
authors.forename: Dafei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. tj6049345@126.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. Liang679@163.com.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. xiaozhan063@163.com.
authors.forename: Xiaozhan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150000, China. yinhang_marine@126.com.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. whx450650@163.com.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. liuchunguo@caas.cn.
authors.forename: Chunguo
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. gdongchun@126.com.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Guo
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. lizhijie.1982@126.com.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. jiangqian623@sina.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. neauljs@163.com.
authors.forename: Jiasen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping road, Xiangfang District, Harbin 150000, China. qld@hvri.ac.cn.
authors.forename: Liandong
authors.initials: L
authors.lastname: Qu
mesh_terms: D000818:Animals; D002415:Cats; D028301:Feline Panleukopenia Virus / Q000276:immunology*; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases
keywords: Feline panleucopenia virus (FPV); Nonstructural protein 2 (NS2); interferon β (IFN-β)