Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals.
Both intranasal (i.n.) and intracerebral (i.c.) inoculation of mice with wild-type equine herpesvirus type 1 (wt EHV-1) caused clinical signs and mortality. Virus could be recovered from target organs (turbinates, lungs and blood) for several days. By contrast, the thymidine kinase (TK)-deficient deletion mutant PR1 produced markedly less clinical disease following both i.n. and i.c. inoculation, and, in particular, no mortality occurred. PR1 did, however, establish productive infections following either route of inoculation. High titres of virus were recovered from target organs although virus did not persist for as long as wt EHV-1 and no viraemia was detected. Primary i.n. infection of mice with either wt EHV-1 or PR1 protected against subsequent challenge with wt EHV-1 5 weeks later. I.n. inoculation of specific pathogen-free (EHV-free) foals with PR1 produced results similar to those observed after infection of mice. Clinical signs were milder than for wt EHV-1 and pyrexia was short-lived or absent. PR1 could be recovered from nasal mucus at high titres but it persisted for only 5 days post-infection compared to 11 days in the case of wt EHV-1. No viraemia was detected in foals infected with PR1. On challenge with wt EHV-1, foals given a primary infection with the mutant were partially protected; but a viraemia with a TK+ EHV-1 was observed. These results demonstrate that our TK- mutant PR1 is markedly less pathogenic than wt EHV-1, despite being able to replicate in the host. The use of TK-deficient mutants of EHV-1 as potential vaccines in the horse is discussed.
Department of Veterinary Medicine, University of Cambridge, U.K.
J D
JD
Slater
J S
JS
Gibson
H J
HJ
Field
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002540:Cerebral Cortex / Q000382:microbiology; D005260:Female; D006566:Herpesviridae Infections / Q000382:microbiology*; D004861:Herpesvirus 1, Equid / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D006736:Horses; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009297:Nasal Mucosa / Q000382:microbiology; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D013937:Thymidine Kinase