title: Attenuation of dUTPase-deficient pseudorabies virus for the natural host.
abstract: 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.
authors.affiliation: Institute of Molecular and Cellular Virology, Friedrich-Loeffler-Institutes, Federal Research Centre for Virus Diseases of Animals, Insel Riems, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Jöns
authors.forename: V
authors.initials: V
authors.lastname: Gerdts
authors.forename: E
authors.initials: E
authors.lastname: Lange
authors.forename: V
authors.initials: V
authors.lastname: Kaden
authors.forename: T C
authors.initials: TC
authors.lastname: Mettenleiter
mesh_terms: D000818:Animals; D011558:Herpesvirus 1, Suid / Q000201:enzymology / Q000235:genetics*; D011557:Pseudorabies / Q000276:immunology / Q000821:virology*; D011755:Pyrophosphatases / Q000172:deficiency* / Q000235:genetics; D013552:Swine; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D014765:Viral Vaccines; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase