An experimental
infection with bovine herpesvirus-1 was established in calves by means of intranasal inoculation. Three calves were infected with the parental strain BHV-1 w/t, three with the TK-defective strain, B 1 and four with the
HPMPA-resistant strain, 3 A. Inoculation with w/t virus resulted in a reproducible clinical disease characterised by respiratory distress,
fever and the presence of virus in nasal mucus. Following the acute
infection, w/t-inoculated animals became seropositive for BHV-1 specific antibody. The TK-defective mutant (BHV-1 B 1) produced an acute
infection similar to the parental virus in all three calves inoculated. The
HPMPA-resistant mutant (BHV-1 3 A), however, showed a reduced pattern of
infection and virus of lower titre was isolated from three of four calves; the antibody responses were generally lower, and one calf remained seronegative until reactivation. Following stimulation with
dexamethasone 72 days after the primary inoculation, virus was re-isolated from all wild type-inoculated calves. In contrast, no evidence of reactivation was obtained from the three B 1-inoculated animals. However, all four animals inoculated with the mutant 3 A showed virus reactivation including the calf which had remained seronegative following primary virus inoculation. Previous studies have suggested that drug-resistance mutations in herpesviruses frequently are associated with reduced pathogenicity on the basis of experiments in laboratory models. The importance of the present study is the demonstration that two different
drug-resistant variants of an alpha herpesvirus both have altered pathogenicity in the natural host for that
infection. These results also have implications for the design and use of
attenuated vaccine strains.