ATTENUATION OF DUTPASE-DEFICIENT PSEUDORABIES VIRUS FOR THE NATURAL HOST

Pseudorabies virus (PrV) is the causative agent of Aujeszky's disease which results in significant losses in pig husbandry. Recently we iden tified the gene encoding the deoxyuridine-triphosphatase (dUTPase) of PrV as the homolog of the UL50 gene of herpes simplex virus type 1. Th e PrV UL50 gene product was characterized and a UL50 negative PrV muta nt (PrV UL50(-)) was generated by insertion of a lacZ expression casse tte into the UL50 open reading frame (Jons and Mettenleiter, J. Virol. 70, 1242-1245). Here we show that replication of PrV UL50(-) in cell culture was only slightly impaired as compared to wild-type PrV strain Ka. After intranasal infection of young pigs PrV UL50(-) proved to be substantially attenuated, whereas severe clinical signs and death occ urred after infection with wild-type PrV. Challenge infection with the highly virulent NIA-3 strain of PrV showed that prior infection with PrV UL50(-) conferred protection against Aujeszky's disease, Innocuity and efficacy make UL50-negative PrV an attractive candidate for a liv e PrV vaccine.