Kasem Samy, Abdel-Moneim Ahmed S, Fukushi Hideto
Department of Virology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.
Laboratory of Veterinary Microbiology, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Virus Genes. 2025 Apr;61(2):179-192. doi: 10.1007/s11262-024-02128-w. Epub 2024 Dec 16.
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.
先前的研究表明，在包括马疱疹病毒1型（EHV-1）在内的几种甲型疱疹病毒中删除病毒胸苷激酶（TK）基因会降低其毒力。此前，我们发现与TK头对头排列的ORF37的缺失会降低EHV-1在小鼠中的毒力，但不影响TK mRNA的表达。因此，ORF38的缺失也可能通过部分删除ORF37启动子而影响毒力。为了研究TK基因编码区在EHV-1发病机制中的作用以及ORF37的表达，我们使用携带神经致病性菌株Ab4p的细菌人工染色体构建了一个TK缺失突变体。TK的缺失增加了ORF37的转录，在CBA/N1小鼠中未引起任何神经疾病，并且其在培养的神经细胞中的生长受到损害。这些结果表明ORF38的缺失不影响ORF37启动子，并证实TK在EHV-1的神经致病性中起重要作用。
