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 identified the gene encoding the deoxyuridine-triphosphatase (dUTPase) of PrV as the homolog of the UL50 gene of herpes simplex virus type 1. The PrV UL50 gene product was characterized and a UL50 negative PrV mutant (PrV UL50−) was generated by insertion of a lacZ expression cassette into the UL50 open reading frame (Jöns 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 occurred 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 live PrV vaccine.