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Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING

1
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
2
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150000, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Joanna Parish
Viruses 2017, 9(1), 23; https://doi.org/10.3390/v9010023
Received: 23 November 2016 / Revised: 17 January 2017 / Accepted: 18 January 2017 / Published: 23 January 2017
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: Feline panleucopenia virus (FPV); Nonstructural protein 2 (NS2); interferon β (IFN-β) Feline panleucopenia virus (FPV); Nonstructural protein 2 (NS2); interferon β (IFN-β)
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Kang, H.; Liu, D.; Tian, J.; Hu, X.; Zhang, X.; Yin, H.; Wu, H.; Liu, C.; Guo, D.; Li, Z.; Jiang, Q.; Liu, J.; Qu, L. Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING. Viruses 2017, 9, 23.

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