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Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/51769

Title: Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B
Authors: Tamura, Tomokazu Browse this author
Sakoda, Yoshihiro Browse this author →KAKEN DB
Yoshino, Fumi Browse this author
Nomura, Takushi Browse this author
Yamamoto, Naoki Browse this author
Sato, Yuka Browse this author
Okamatsu, Masatoshi Browse this author →KAKEN DB
Ruggli, Nicolas Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Issue Date: Aug-2012
Publisher: American Society for Microbiology
Journal Title: Journal of Virology
Volume: 86
Issue: 16
Start Page: 8602
End Page: 8613
Publisher DOI: 10.1128/JVI.00551-12
Abstract: Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low virulent and moderate virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE- was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE- vaccine virus was re-adapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE-/P-11 virus isolated from the tonsils after the 11th passage in vivo had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) when compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies in vitro indicated that the substitution in E2 influenced virus spreading, and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency in vitro and pathogenicity in pigs.
Rights: © 2012 American Society for Microbiology
Type: article (author version)
URI: http://hdl.handle.net/2115/51769
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: 田村 友和

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