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Ribonucleotide reductase-deficient mutants of pseudorabies virus are avirulent for pigs and induce partial protective immunity

Niels de Wind^1,

¹ Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam
and² Department of Virology of the Central Veterinary Institute, P.O. Box 365, 8200 AJ Lelystad, The Netherlands

We have mutagenized and mapped the gene encoding the large subunit of ribonucleotide reductase (RR₁) in pseudorabies virus (PRV; synonyms Aujeszky's disease virus, suid herpesvirus type 1). PRV strains carrying an oligonucleotide that leads to termination of translation of the RR₁ gene are avirulent for mice. We subsequently constructed a PRV strain carrying a deletion in the RR₁ gene and also a PRV strain carrying both the deletion in the RR₁ gene and a deletion in the glycoprotein g1 gene, which is a marker for PRV virulence. Both PRV strains were assayed for virulence and immunogenicity in pigs, the natural host for PRV. In contrast to a marker-rescued PRV strain, these RR₁-deleted mutants were avirulent, were shed in very low titres in the oropharyngeal fluid by the animals, and induced low titres of neutralizing antibodies. However, protection against clinical signs after infection with virulent PRV was induced by both RR₁-deleted mutants. The relative importance of viral RR and thymidine kinase enzymes for deoxynucleotide synthesis in viral replication is discussed. In addition, we discuss the potential use of RR as a target for anti-herpesviral drugs and the use of PRV strains, deleted for the RR₁ gene, as vaccine strains.

Present address: Laboratory of Mutagenesis, Jacques Monod Institute, 2 Place Jussieu, 75251 Paris Cedex 05, France

Received 13 July 1992; accepted 19 October 1992.

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