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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

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Title: 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
Authors: Itakura, Yukari Browse this author
Matsuno, Keita Browse this author →KAKEN DB
Ito, Asako Browse this author
Gerber, Markus Browse this author
Liniger, Matthias Browse this author
Fujimoto, Yuri Browse this author
Tamura, Tomokazu Browse this author
Kameyama, Ken-ichiro Browse this author
Okamatsu, Masatoshi Browse this author →KAKEN DB
Ruggli, Nicolas Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Sakoda, Yoshihiro Browse this author →KAKEN DB
Keywords: Classical swine fever virus
Type-I interferon
Issue Date: 15-Jan-2020
Publisher: Elsevier
Journal Title: Virus Research
Volume: 276
Start Page: 197809
Publisher DOI: 10.1016/j.virusres.2019.197809
PMID: 31715204
Abstract: 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.
Rights: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 迫田 義博

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