Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents

Walid Azab, Koji Tsujimura, Kentaro Kato, Jun Arii, Tomomi Morimoto, Yasushi Kawaguchi, Yukinobu Tohya, Tomio Matsumura, Hiroomi Akashi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79ΔTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied by means of a plaque reduction assay. GCV proved to be more potent and showed a superior anti-EHV-4 activity. On the other hand, ACV showed very poor ability to inhibit EHV-4 replication. As predicted, WA79ΔTK was insensitive to GCV. Although EHV-4 is normally insensitive to ACV, it showed >20-fold increase in sensitivity when the equine herpesvirus-1 (EHV-1) TK was supplied in trans. Furthermore, both ACV and GCV resulted in a significant reduction of plaque size induced by EHV-4 and 1. Taken together, these data provided direct evidence that GCV is a potent selective inhibitor of EHV-4 and that the virus-encoded TK is an important determinant of the virus susceptibility to nucleoside analogues.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalAntiviral Research
Volume85
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1
Externally publishedYes

Keywords

  • Antiviral drugs
  • EHV-4
  • TK

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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