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Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in N-pro responsible for inhibition of type I interferon production

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Title: Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in N-pro responsible for inhibition of type I interferon production
Authors: Kozasa, Takashi Browse this author →KAKEN DB
Abe, Yuri Browse this author
Mitsuhashi, Kazuya Browse this author
Tamura, Tomokazu Browse this author
Aoki, Hiroshi Browse this author →KAKEN DB
Ishimaru, Masatoshi Browse this author
Nakamura, Shigeyuki Browse this author
Okamatsu, Masatoshi Browse this author →KAKEN DB
Kida, Hiroshi Browse this author →KAKEN DB
Sakoda, Yoshihiro Browse this author →KAKEN DB
Keywords: bovine viral diarrhea virus
END phenomenon
interferon regulatory factor-3
N-pro
type I interferon
Issue Date: May-2015
Publisher: 日本獣医学会
Journal Title: Journal of Veterinary Medical Science
Volume: 77
Issue: 5
Start Page: 511
End Page: 518
Publisher DOI: 10.1292/jvms.14-0420
Abstract: The Exaltation of Newcastle disease virus (END) phenomenon is induced by the inhibition of type I interferon in pestivirus-infected cells in vitro, via proteasomal degradation of cellular interferon regulatory factor (IRF)-3 with the property of the viral autoprotease protein N-pro. Reportedly, the amino acid residues in the zinc-binding TRASH motif of N-pro determine the difference in characteristics between END-phenomenon-positive (END) and END-phenomenon-negative (END-) classical swine fever viruses (CSFVs). However, the basic mechanism underlying this function in bovine viral diarrhea virus (BVDV) has not been elucidated from the genomic differences between END+ and END- viruses using reverse genetics till date. In the present study, comparison of complete genome sequences of a pair of END+ and END- viruses isolated from the same virus stock revealed that there were only four amino acid substitutions (D136G, I2623V, D3148G and D3502Y) between two viruses. Based on these differences, viruses with and without mutations at these positions were generated using reverse genetics. The END assay, measurements of induced type I interferon and IRF-3 detection in cells infected with these viruses revealed that the aspartic acid at position 136 in the zinc-binding TRASH motif of N-pro was required to inhibit the production of type I interferon via the degradation of cellular IRF-3, consistently with CSFV.
Rights: http://creativecommons.org/licenses/by-nc-nd/3.0/
Type: article
URI: http://hdl.handle.net/2115/59589
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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