Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have amplified, cloned and sequenced the gene encoding the thymidine kinase (TK) of a wild-type strain (Ab4) of equine herpesvirus-1 (EHV-1) and two mutants with defective TK activity isolated for resistance to penciclovir (PCV). One of the mutants, PR1, has suffered a 879-bp deletion which reduces the size of TK to 180 bp. The other mutant, PR3, has an adenine to cytosine mutation resulting in a Lys38-->Thr change. This mutation modifies the amino acid sequence of a domain involved in binding ATP, leading to non-detectable enzymatic activity. Lys38 thus appears to be essential for the activity of the TK of EHV-1.
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PMID:Sequence analysis of thymidine kinase-defective mutants of equine herpesvirus-1 (EHV-1). 838 60

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.
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PMID:Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals. 838 18