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N-pro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites

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Title: N-pro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites
Authors: Tamura, Tomokazu Browse this author
Nagashima, Naofumi Browse this author
Ruggli, Nicolas Browse this author
Summerfield, Artur Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Sakoda, Yoshihiro Browse this author →KAKEN DB
Issue Date: 17-Apr-2014
Publisher: BioMed Central
Journal Title: Veterinary Research
Volume: 45
Publisher DOI: 10.1186/1297-9716-45-47
Abstract: Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The viral protein N-pro of CSFV interferes with alpha-and beta-interferon (IFN-alpha/beta) induction by promoting the degradation of interferon regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF vaccine strain GPE(-), N-pro acquired a mutation that abolished its capacity to bind and degrade IRF3, rendering it unable to prevent IFN-alpha/beta induction. In a previous study, we showed that the GPE(-) vaccine virus became pathogenic after forced serial passages in pigs, which was attributed to the amino acid substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B. Interestingly, during the re-adaptation of the GPE(-) vaccine virus in pigs, the IRF3-degrading function of N-pro was not recovered. Therefore, we examined whether restoring the ability of N-pro to block IFN-alpha/beta induction of both the avirulent and moderately virulent GPE(-)-derived virus would enhance pathogenicity in pigs. Viruses carrying the N136D substitution in N-pro regained the ability to degrade IRF3 and suppress IFN-alpha/beta induction in vitro. In pigs, functional N-pro significantly reduced the local IFN-alpha mRNA expression in lymphoid organs while it increased quantities of IFN-alpha/beta in the circulation, and enhanced pathogenicity of the moderately virulent virus. In conclusion, the present study demonstrates that functional N-pro influences the innate immune response at local sites of virus replication in pigs and contributes to pathogenicity of CSFV in synergy with viral replication.
Rights: http://creativecommons.org/licenses/by-nc-sa/2.1/jp/
Type: article
URI: http://hdl.handle.net/2115/56413
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 迫田 義博

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