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Npro of Classical Swine Fever Virus Suppresses Type III Interferon Production by Inhibiting IRF1 Expression and Its Nuclear Translocation

1
Institute of Preventive Veterinary Medicine, Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China
2
Experimental Animal Center of Zhejiang Academy of Medical Sciences, Hangzhou 310013, China
3
Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2019, 11(11), 998; https://doi.org/10.3390/v11110998
Received: 1 September 2019 / Revised: 25 October 2019 / Accepted: 29 October 2019 / Published: 31 October 2019
(This article belongs to the Section Animal Viruses)
Classical swine fever virus (CSFV) causes a contagious disease of pigs. The virus can break the mucosal barrier to establish its infection. Type III interferons (IFN-λs) play a crucial role in maintaining the antiviral state in epithelial cells. Limited information is available on whether or how CSFV modulates IFN-λs production. We found that IFN-λ3 showed dose-dependent suppression of CSFV replication in IPEC-J2 cells. Npro-deleted CSFV mutant (∆Npro) induced significantly higher IFN-λs transcription from 24 h post-infection (hpi) than its parental strain (wtCSFV). The strain wtCSFV strongly inhibited IFN-λs transcription and IFN-λ3 promoter activity in poly(I:C)-stimulated IPEC-J2 cells, whereas ∆Npro did not show such inhibition. Npro overexpression caused significant reduction of IFN-λs transcription and IFN-λ3 promoter activity. Both wtCSFV and ∆Npro infection induced time-dependent IRF1 expression in IPEC-J2 cells, with ΔNpro showing more significant induction, particularly at 24 hpi. However, infection with wtCSFV or Npro overexpression led not only to significant reduction of IRF1 expression and its promoter activity in poly(I:C)-treated IPEC-J2 cells but also to blockage of IRF1 nuclear translocation. This study provides clear evidence that CSFV Npro suppresses IRF1-mediated type III IFNs production by inhibiting IRF1 expression and its nuclear translocation. View Full-Text
Keywords: classical swine fever virus; Type III interferons; Npro; IRF1 classical swine fever virus; Type III interferons; Npro; IRF1
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MDPI and ACS Style

Cao, T.; Li, X.; Xu, Y.; Zhang, S.; Wang, Z.; Shan, Y.; Sun, J.; Fang, W.; Li, X. Npro of Classical Swine Fever Virus Suppresses Type III Interferon Production by Inhibiting IRF1 Expression and Its Nuclear Translocation. Viruses 2019, 11, 998.

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