Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle

We previously reported that the bovine herpesvirus 1 (BHV 1) gene homologous to herpes simplex virus gene UL49 is dispensable; nevertheless, a mutant with the UL49 homolog (UL49h) gene deletion exhibited significantly impaired growth in cell culture. To further evaluate the role of the UL49h in virus infectivity in the natural host of BHV 1, the pathogenesis of the UL49h negative mutant was studied in cattle. An additional mutant with a combined defect in UL49h, UL49.5h and dUTPase genes was also studied in parallel. We found that both mutants were avirulent in cattle inasmuch as intranasal (i.n.) administration of either mutants induced no apparent clinical disease, nor did animals receiving the mutants shed virus. Following i.n. inoculation with the mutants animals developed low levels of serum neutralizing (SN) antibodies, and were partially protected against wild-type BHV 1 challenge. Intramuscular immunizations with either mutant induced good SN titers, and moreover, they induced nearly complete protection against respiratory challenge with wild-type virus. The results from this study establish that BHV 1 UL49h is an important virulence factor, and also suggest that deletion of the nonessential viral genes UL49h, UL49.5h and dUTPase may be useful in developing recombinant BHV 1 vaccines or BHV 1-based vaccine vectors.