Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals.
Abstract: 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.
Publication Date: 1993-05-01 PubMed ID: 8388018DOI: 10.1099/0022-1317-74-5-819Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates the less harmful effects of a modified equine herpesvirus type 1 (EHV-1) compared to the wild-type version in mice and specific-pathogen-free foals. It also assesses the potential of this modified virus (named PR1) as a vaccine against the wild type.
Research Context
- The research aims to understand the behavior of a modified version of equine herpesvirus type 1 (EHV-1) in comparison with the original, more pathogenic version of the virus.
- The modified virus is a thymidine kinase (TK) deficient mutant labeled as PR1. Thymidine kinase is a type of enzyme that is crucial for virus replication, and its deficiency in the PR1 variant is intended to reduce the harmful impact on infected subjects.
Experimental Design and Findings
- Mice were subjected to both intranasal (i.n.) and intracerebral (i.c.) inoculation with the wild-type EHV-1 and the TK-deficient PR1.
- Wild-type EHV-1 caused disease symptoms and death in mice, with the virus being recoverable from their organic systems for several days after infection.
- Conversely, mice infected with PR1 exhibited significantly milder disease symptoms, no death was observed, the virus was recoverable at high levels but did not persist as long, and no incidence of viraemia (presence of the virus in the blood) was detected.
- Mice initially inoculated with either the wild-type or PR1 were found to be protected against subsequent exposure to the wild-type virus 5 weeks later.
- These experimental procedures were similarly conducted with specific-pathogen-free (EHV-free) foals. Foals inoculated with PR1 were found to be partially protected against the wild-type version of the virus, although a viraemia involving the wild-type virus was noticed.
Conclusions and Implications
- The researchers concluded that the thymidine kinase-deficient PR1 mutant of the EHV-1 virus was less pathogenic despite being able to replicate within the host organism.
- This study suggests the potential use of TK-deficient mutants like PR1 as potential vaccines for equines against the more harmful wild viral strains.
- The exploration of how these TK-deficient viruses might be developed into effective, mass-producible vaccines is a matter of further research.
Cite This Article
APA
Slater JD, Gibson JS, Field HJ.
(1993).
Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals.
J Gen Virol, 74 ( Pt 5), 819-828.
https://doi.org/10.1099/0022-1317-74-5-819 Publication
Researcher Affiliations
- Department of Veterinary Medicine, University of Cambridge, U.K.
MeSH Terms
- Animals
- Animals, Newborn
- Cell Line
- Cerebral Cortex / microbiology
- Female
- Herpesviridae Infections / microbiology
- Herpesvirus 1, Equid / enzymology
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / pathogenicity
- Horses
- Mice
- Mice, Inbred BALB C
- Mutation
- Nasal Mucosa / microbiology
- Rabbits
- Specific Pathogen-Free Organisms
- Thymidine Kinase / genetics
- Thymidine Kinase / metabolism
Citations
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