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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BORIS DOI
Date of Publication
January 15, 2020
Publication Type
Article
Division/Institute
Author
Itakura, Yukari | |
Matsuno, Keita | |
Ito, Asako | |
Fujimoto, Yuri | |
Tamura, Tomokazu | |
Kameyama, Ken-Ichiro | |
Okamatsu, Masatoshi | |
Kida, Hiroshi | |
Sakoda, Yoshihiro |
Series
Virus research
ISSN or ISBN (if monograph)
0168-1702
Publisher
Elsevier
Language
English
Publisher DOI
PubMed ID
31715204
Uncontrolled Keywords
Description
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 Npro-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 Npro function was restored to inhibit type-I IFN induction did not induce necroptosis nor CPE but still induced apoptosis, while an Npro-mutant vALD-A76 incapable of inhibiting type-I IFN production induced necroptosis and CPE. Although Erns 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 Erns of these two strains. Altogether, these results demonstrate that type-I IFN-dependent necroptosis related to non-functional Npro is the main mechanism for CPE induction by vGPE-, and that viral factor(s) other than Erns may induce or inhibit apoptosis in vGPE- or vALD-A76 infected CPK-NS cells, respectively.