Functional analysis of the UL24 protein of suid herpesvirus 1

文献类型： 外文期刊

第一作者： Ye, Chao

作者： Ye, Chao;Chen, Jing;Cheng, Xuefei;Zhou, Shasha;Jiang, Shan;Xu, Jingjing;Zheng, Hao;Tong, Wu;Li, Guoxin;Tong, Guangzhi;Zheng, Hao;Tong, Wu;Li, Guoxin;Tong, Guangzhi

作者机构：

关键词： Suid herpesvirus 1; UL24; Thymidine kinase; CRISPR; Cas9; Virulence

期刊名称：VIRUS GENES （ 影响因子：2.332； 五年影响因子：2.0 ）

ISSN： 0920-8569

年卷期： 2019 年 55 卷 1 期

页码：

收录情况： SCI

摘要： The UL24 homologous genes are conserved in alphaherpesviruses. However, the proximity of the UL24 gene and the UL23 gene encoding for thymidine kinase (TK) in the genome of suid herpesvirus 1 (SuHV-1) makes it difficult to mutate UL24 without affecting the expression of the TK gene, and thus functional studies of the UL24 gene have lagged behind. In this study, CRISPR/Cas9 and homologous recombination were adopted to generate UL24 and TK mutant viruses. Deletion of either the UL24 or the TK gene resulted in significantly reduced SuHV-1 replication and spread capacity in Vero cells. However, UL24-deleted virus still maintained a certain degree of lethality in mice, while TK-deleted viruses completely lost their lethality in mice. Similarly, neurovirulence of UL24-deleted virus in mice was not significantly affected compared to parental virus. In comparison, infection with the TK-deleted viruses resulted in significantly reduced neurovirulence and complete loss of lethality. In addition, and for the first time, viral UL24 protein was found to be expressed late during SuHV-1 infection; enhanced green fluorescence protein (eGFP) labeled UL24 protein was shown to be localized in the nucleus via heterologous expression. In conclusion, the UL24 gene of SuHV-1 encodes a nuclear-localized viral protein and acts as a minor virulence-associated factor compared to the TK gene.

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