Effect of thymidine kinase-deficiency (∆ORF38) on neuropathogenicity of equine herpesvirus-1 in the mouse model and expression of neighboring genes.

Abstract

Previous studies showed that deletion of the viral thymidine kinase (TK) gene in several alphaherpesviruses including EHV-1 reduced their virulence. Previously, we found that deletion of ORF37, which is located head-to-head with TK, decreased EHV-1 virulence in mice but did not affect the expression of TK mRNA. Therefore, deletion of ORF38 might also affect virulence by partially deleting the ORF37 promoter. To investigate the role of the TK gene-encoding region in the pathogenesis of EHV-1 as well as the expression of ORF37, we generated a TK deletion mutant by using a bacterial artificial chromosome carrying the neuropathogenic strain Ab4p. Deletion of TK increased the transcription of ORF37, did not cause any neurological disorders in CBA/N1 mice, and its growth in cultured neural cells was impaired. These results suggest deletion of ORF38 does not affect the ORF37 promoter and confirm that TK plays an important role in the neuropathogenicity of EHV-1.