Cyprinid herpesvirus 3 replication is inhibited via decreased ORF3 promoter activity mediated by multiple cellular transcription factors

文献类型： 外文期刊

第一作者： Liu, Donghai

作者： Liu, Donghai;Wang, Yingying;Li, Yingying;Mo, Xubing;Yin, Jiyuan;Wang, Qing;Zheng, Shucheng;Liu, Donghai

作者机构：

关键词： Cyprinid herpesvirus 3; Koi herpesvirus; ORF3; Promoter; Transcription factors

期刊名称：AQUACULTURE （ 影响因子：3.9； 五年影响因子：4.4 ）

ISSN： 0044-8486

年卷期： 2025 年 595 卷

页码：

收录情况： SCI

摘要： Cyprinid herpesvirus 3 (CyHV-3) is an enveloped and double-stranded DNA virus that primarily infects common carp and its variants. The transcriptional regulation program of the viral immediate early (IE) genes plays a crucial role in virus replication. However, the transcriptional regulatory mechanism of CyHV-3 IE genes remains largely unclear. In this study, we found that the IE gene ORF3 promoter, which exhibited the highest activity among the eight CyHV-3 IE genes, was inhibited in the host common carp brain (CCB) cells. Deletions of the ORF3 promoter revealed the presence of multiple regulatory elements. Site-directed deletions of multiple transcription factors binding sites (TFBS), including Yin Yang-1(YY1), TATA-binding protein (TBP), sex-determining region Y-box2 (SOX2), and cyclin-dependent kinase 8 (CDK8) binding sites, markedly inhibited the ORF3 promoter activity. Moreover, overexpression of these transcription factors in CCB cells also led to a noticeable reduction in ORF3 promoter activity. Importantly, YY1, TBP, SOX2, and CDK8 played antiviral roles against CyHV-3 infection, as evidenced by decreased viral transcripts ( ORF55 , ORF81, and ORF92) ) and genome copies after overexpression of these TFs followed by CyHV-3 infection. Collectively, CyHV-3 replication was markedly inhibited by reducing the promoter activity of ORF3 mediated by multiple cellular TFs. These findings enhance our understanding of the role of IE gene promoters in CyHV-3 and lays a foundation for in-depth studies on viral gene transcriptional regulation mechanisms.

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