Gilliam S E, Thackray A M, Brown G A, Field H J
Department of Clinical Veterinary Medicine, Cambridge, U.K.
Arch Virol. 1993;128(1-2):43-54. doi: 10.1007/BF01309787.
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.
通过鼻内接种的方式在犊牛中建立了牛疱疹病毒-1的实验性感染。三只犊牛感染了亲本毒株BHV-1 w/t，三只感染了胸苷激酶缺陷型毒株B 1，四只感染了对磷甲酸钠耐药的毒株3 A。接种野生型病毒导致了一种可重现的临床疾病，其特征为呼吸窘迫、发热以及鼻黏液中存在病毒。急性感染后，接种野生型病毒的动物对BHV-1特异性抗体呈血清阳性。胸苷激酶缺陷型突变体（BHV-1 B 1）在所有三只接种的犊牛中引发了与亲本病毒相似的急性感染。然而，对磷甲酸钠耐药的突变体（BHV-1 3 A）显示出感染模式减弱，并且从四只犊牛中的三只分离出了滴度较低的病毒；抗体反应通常较低，并且一只犊牛在重新激活之前一直保持血清阴性。在初次接种72天后用地塞米松刺激后，从所有接种野生型病毒的犊牛中再次分离出了病毒。相比之下，在三只接种B 1的动物中未获得重新激活的证据。然而，所有四只接种突变体3 A的动物都出现了病毒重新激活，包括在初次接种病毒后一直保持血清阴性的犊牛。先前的研究表明，基于实验室模型实验，疱疹病毒中的耐药突变通常与致病性降低有关。本研究的重要性在于证明了α疱疹病毒的两种不同耐药变体在该感染的天然宿主中均具有改变的致病性。这些结果也对减毒疫苗株的设计和使用具有启示意义。
