Attenuation of classical swine fever virus by deletion of the viral N(pro) gene.
We have reported earlier that replacement of the N(pro) gene of classical swine fever virus (CSFV) by the murine ubiquitin gene only slightly affects the characteristics of virus replication in the porcine kidney cell line SK-6 [J. Virol. 72 (1998) 7681]. Here, for the moderately virulent CSFV strain Alfort/187 as well as for the highly virulent strain Eystrup we show that the respective N(pro)-deleted viruses are attenuated. Vaccination of pigs with either of the two deletion mutants resulted in the induction of a strong antibody response. Animals were protected against challenge with a lethal dose of highly virulent CSFV indicating that N(pro) deletion mutants are excellent candidates for a modified live virus vaccine. A chimeric virus obtained by replacement of the N(pro) gene in the Eystrup virus by the corresponding sequence of the avirulent CSFV vaccine strain Riems resulted in a virus that was highly virulent. This indicates that the virulence of CSFV correlates with the presence of N(pro) and also suggests that N(pro) is not responsible for the varying virulence observed between individual strains of CSFV.
Mayer
Daniel
D
Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
Hofmann
Martin A
MA
Tratschin
Jon Duri
JD
D000818:Animals; D002460:Cell Line; D006691:Classical Swine Fever / Q000517:prevention & control / Q000821:virology; D006692:Classical Swine Fever Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D003001:Cloning, Molecular; D005814:Genes, Viral / Q000235:genetics* / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D012313:RNA / Q000096:biosynthesis; D013552:Swine; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D025801:Ubiquitin / Q000235:genetics; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D025801:Ubiquitin; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D037521:Virulence Factors; D012313:RNA