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Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B
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)
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Submitter: 田村 友和
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