A cloned classical swine fever virus derived from the vaccine strain GPE causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis

Itakura, Yukari; Matsuno, Keita; Ito, Asako; Gerber, Markus; Liniger, Matthias; Fujimoto, Yuri; Tamura, Tomokazu; Kameyama, Ken-ichiro; Okamatsu, Masatoshi; Ruggli, Nicolas; Kida, Hiroshi; Sakoda, Yoshihiro

A cloned classical swine fever virus derived from the vaccine strain GPE causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis

Itakura, Yukari; Matsuno, Keita; Ito, Asako et al.

Virus Research, 2020, 276, 197809

Permalink : https://hdl.handle.net/2115/80229

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/80229
タイトル	A cloned classical swine fever virus derived from the vaccine strain GPE causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis
著者	Itakura, Yukari ; Matsuno, Keita ; Ito, Asako ; Gerber, Markus ; Liniger, Matthias ; Fujimoto, Yuri ; Tamura, Tomokazu ; Kameyama, Ken-ichiro ; Okamatsu, Masatoshi ; Ruggli, Nicolas ; Kida, Hiroshi ; Sakoda, Yoshihiro
著者名 Itakura, Yukari
e-Rad_Researcher 40753306 著者名 Matsuno, Keita
著者名 Ito, Asako
著者名 Gerber, Markus
著者名 Liniger, Matthias
著者名 Fujimoto, Yuri
著者名 Tamura, Tomokazu
著者名 Kameyama, Ken-ichiro
e-Rad_Researcher 00507163 著者名 Okamatsu, Masatoshi
著者名 Ruggli, Nicolas
e-Rad_Researcher 10109506 著者名 Kida, Hiroshi
e-Rad_Researcher 40333637 著者名 Sakoda, Yoshihiro
言語	英語
キーワード	Classical swine fever virus
	Necroptosis
	Apoptosis
	Type-I interferon
発行日	2020-01-15
出版者	Elsevier
収録物名	Virus Research
巻(号)	276
ページ	197809
抄録	Classical swine fever viruses (CSFVs) do typically not show cytopathic effect (CPE) in cell culture, while some strains such as vaccine strain the GPE(-) induce CPE in the swine kidney-derived CPK-NS cell line cultured in serum-free medium. These latter strains commonly lack N-pro-mediated inhibition of type-I interferon (IFN) induction. In order to explore the molecular mechanisms of GPE(-)-induced CPE, we analyzed the cellular pathways involved. In CPK-NS cells infected with the attenuated-vaccine-derived vGPE(-) strain, both, apoptosis and necroptosis were induced. Necroptosis was type-I IFN-dependent and critical for visible CPE. In contrast, the parental virulent vALD-A76 strain did not induce any of these pathways nor CPE. We used reverse genetics to investigate which viral factors regulate these cell-death pathways. Interestingly, a mutant vGPE(-) in which the N-pro function was restored to inhibit type-I IFN induction did not induce necroptosis nor CPE but still induced apoptosis, while an N-Pro-mutant vALD-A76 incapable of inhibiting type-I IFN production induced necroptosis and CPE. Although E-rns of CSFV is reportedly involved in controlling apoptosis, apoptosis induction by vGPE(-) or apoptosis inhibition by vALD-A76 were independent of the unique amino acid difference found in EP's of these two strains. Altogether, these results demonstrate that type-I IFN-dependent necroptosis related to non-functional N-pro is the main mechanism for CPE induction by vGPE(-), and that viral factor(s) other than E-rns may induce or inhibit apoptosis in vGPE(-) or vALD-A76 infected CPK-NS cells, respectively.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0168-1702
EISSN	1872-7492
NCID	AA10642076
関連情報	PMID 31715204
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.virusres.2019.197809