Attenuation of classical swine fever virus by deletion of the viral Npro 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) 768 1]. 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. (C) 2003 Elsevier Ltd. All rights reserved.