STUDY OF IMMUNOGENICITY AND VIRULENCE OF BOVINE HERPESVIRUS-1 MUTANTSDEFICIENT IN THE UL49 HOMOLOG, UL49.5 HOMOLOG AND DUTPASE GENES IN CATTLE

We previously reported that the bovine herpesvirus 1 (BHV 1) gene homo logous to herpes simplex virus gene UL49 is dispensable; nevertheless, a mutant with the UL49 homolog (UL49h) gene deletion exhibited signif icantly impaired growth in cell culture. To further evaluate tile role of the UL49h in virus infectivity in the natural host of BHV I, the p athogenesis of the UL49h negative mutant was studied in cattle, An add itional mutant with a combined defect in UL49h, UL49.5h and dUTPase ge nes was also studied in parallel, We found that both mutants were avir ulent in cattle inasmuch as intranasal (i.n.) administration of either mutants induced no apparent clinical disease, nor did animals receivi ng the mutants shed virus, Following i.n. inoculation with the mutants animals developed low levels of serum neutralizing (SN) antibodies, a nd were partially protected against wild-type BHV 1 challenge, Intramu scular immunizations with either mutant induced goon SN titers, and mo reover they induced nearly complete protection against respiratory cha llenge with wild-type virus. The results from this study establish tha t BHV 1 UL49h is an important virulence factor and also suggest that d eletion of the nonessential viral genes UL49h, UL49,5h and dUTPase may be useful in developing recombinant BHV 1 vaccines ol BHV 1-based vac cine vectors. (C) 1997 Elsevier Science Ltd.