Molecular characterization, transcriptional regulation of sea perch Moloney leukemia virus 10 and its antiviral function against VHSV.
Molecular characterization, transcriptional regulation of sea perch Moloney leukemia virus 10 and its antiviral function against VHSV.
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DOI：
10.1016/j.fsi.2023.108874
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发表时间：
2023-06
影响因子：
4.7
通讯作者：
Xiaobing Lu;Zhe Hu;Hao Huang;M. Yi;K. Jia
中科院分区：
文献类型：
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作者：
Xiaobing Lu;Zhe Hu;Hao Huang;M. Yi;K. Jia
莫洛尼白血病病毒10（MOV10）是一种保守的RNA解旋酶，在哺乳动物中具有多种生物学功能，但其在硬骨鱼中的作用仍知之甚少。本研究克隆了鲈鱼MOV10基因的一个同源基因，该基因包含23个外显子和22个内含子，开放阅读框为3000 bp，编码1000个氨基酸。组织分布分析表明，MOV10在鲈鱼血液中高表达。启动子分析揭示了几个推定的多转录因子结合位点，包括上游转录因子1，GATA盒，转录起始因子IIB，激活蛋白1和两个干扰素（IFN）刺激的反应元件。进一步分析发现，IFN c、IFN h和IFNγ不仅可以激活IFN调节因子（IRF）1的表达，进而诱导MOV10的表达，而且可以促进IRF 10的表达，从而抑制MOV10的过度表达。此外，IRF2还抑制由IRF1启动的MOV10表达。病毒性出血性败血症病毒（viral hemorrhagic septicemia virus，VHSV）感染可上调体内和体外MOV10的表达，进而上调IFN h的表达，表现出较强的抗VHSV增殖的活性。本研究为探讨VHSV通过影响与抗病毒分子相关的信号通路中转录因子的生物学功能来实现免疫逃逸提供了基础。
Moloney leukemia virus 10 (MOV10) is a conserved RNA helicase and has multiple biological functions in mammals, but its role remains poorly understood in bony fish. Here, we cloned a MOV10 homolog from sea perch (Lateolabrax japonicus), which contained 23 exons and 22 introns, with an open reading frame of 3000 bp encoding 1000 amino acids. Tissue distribution analysis showed that MOV10 was high expressed in blood of sea perch. Promoter analysis revealed several putative multiple transcription factors binding sites, including upstream transcription factor 1, GATA-box, transcription initiation factor IIB, activator protein 1 and two interferon (IFN) stimulated response elements. Further analysis found that IFNc, IFNh, and IFNγ could not only activate IFN regulatory factor (IRF) 1 expression which in turn led to the induction of MOV10, but also prompted the expression of IRF10 to hinder excessive MOV10 expression. Moreover, IRF2 also suppressed MOV10 expression that was initiated by IRF1. Viral hemorrhagic septicemia virus (VHSV) infection upregulated MOV10 expressionin vivoandin vitro, which in turn, enhanced IFNh expression and exhibited strong antiviral activity against VHSV proliferation. This study provides a basis to investigate the immune escape of VHSV by affecting the biological function of transcription factors in the signaling pathways associated with antiviral molecules.