The N-terminal domain of N-pro of classical swine fever virus determines its stability and regulates type I IFN production

Mine Junki; Tamura Tomokazu; Mitsuhashi Kazuya; Okamatsu Masatoshi; Parchariyanon Sujira; Pinyochon Wasana; Ruggli Nicolas; Tratschin Jon-Duri; Kida Hiroshi; Sakoda Yoshihiro

タイトル	en The N-terminal domain of N-pro of classical swine fever virus determines its stability and regulates type I IFN production
作成者	en Mine, Junki en Tamura, Tomokazu en Mitsuhashi, Kazuya en Okamatsu, Masatoshi NRID 1000000507163 en Parchariyanon, Sujira en Pinyochon, Wasana en Ruggli, Nicolas en Tratschin, Jon-Duri en Kida, Hiroshi NRID 1000010109506 en Sakoda, Yoshihiro NRID 1000040333637
アクセス権	open access
主題	Other en CSFV Other en Npro Other ja IFN-α/β Other en stability NDC 491
内容注記	Abstract en The viral protein N-pro is unique to the genus Pestivirus within the family Flaviviridae. After autocatalytic cleavage from the nascent polyprotein, N-pro suppresses type I IFN (IFN-alpha/beta) induction by mediating proteasomal degradation of IFN regulatory factor 3 (IRF-3). Previous studies found that the N-pro-mediated IRF-3 degradation was dependent of a TRASH domain in the C-terminal half of N-pro coordinating zinc by means of the amino acid residues 0112, 0134, D136 and C138. Interestingly, four classical swine fever virus (CSFV) isolates obtained from diseased pigs in Thailand in 1993 and 1998 did not suppress IFN-alpha/beta induction despite the presence of an intact TRASH domain. Through systematic analyses, it was found that an amino acid mutation at position 40 or mutations at positions 17 and 61 in the N-terminal half of N-pro of these four isolates were related to the lack of IRF-3-degrading activity. restoring a histidine at position 40 or both a proline at position 17 and a lysine at position 61 based on the sequence of a functional N-pro contributed to higher stability of the reconstructed N-pro compared with the N-pro from the Thai isolate. This led to enhanced interaction of N-pro with IRF-3 along with its degradation by the proteasome. The results of the present study revealed that amino acid residues in the N-terminal domain of N-pro are involved in the stability of N-pro, in interaction of N-pro with IRF-3 and subsequent degradation of IRF-3, leading to downregulation of IFN-alpha/beta production.
出版者	en Society for General Microbiology
日付	Issued2015-07
言語	eng
資源タイプ	journal article
出版タイプ	AM
資源識別子	HDL http://hdl.handle.net/2115/62343
関連	isVersionOf DOI https://doi.org/10.1099/vir.0.000132 PMID 25809915
収録誌情報	PISSN 0022-1317 EISSN 1465-2099 NCID AA00698722 en Journal of General Virology 巻96 号7 開始ページ1746 終了ページ1756
ファイル	fulltext J.Gen.Virol. v.96 p.1746-1756.pdf 627.88 KB (application/pdf) Issued2015-07 fulltext Supplementary Data.pdf 210.72 KB (application/pdf) Issued2015-07
コンテンツ更新日時	2023-07-26