对于基因组复制,需要在多个保存位置分离E型肝炎病毒多蛋白质的血栓分裂
Danielle M Pierce1, Frazer J T Buchanan1, Fraser L Macrae2
1School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
PLoS pathogens
|July 21, 2023
概括
肝炎E病毒 (HEV) 复制依赖宿主蛋白酶,而不是病毒酶,用于聚蛋白加工. 突变分裂部位或抑制血清蛋白酶会阻止病毒复制,突出显示宿主依赖性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 肝炎研究研究 肝炎研究
背景情况:
- 积极感应RNA病毒,包括肝炎E病毒 (HEV),合成复制必需的多蛋白质.
- 通过蛋白质分解处理多蛋白质会产生功能性病毒蛋白,这是由病毒或宿主蛋白酶调节的关键步骤.
- 在HEV中聚蛋白加工的精确机制在很大程度上仍未被阐明.
研究的目的:
- 研究E型肝炎病毒 (HEV) 聚蛋白加工的机制.
- 确定聚蛋白加工在HEV复制中的作用.
- 探索宿主细胞蛋白酶在HEV多蛋白成熟中的潜在参与.
主要方法:
- 在体外翻译实验以评估聚蛋白加工.
- HEV亚基因组复制系统用于研究病毒复制.
- 生物信息分析以确定潜在的蛋白质酶分裂部位.
- 已识别的切割部位的局部定向突变发生.
- 药理上抑制了血清蛋白酶的作用.
主要成果:
- 试验室翻译结果主要是未经加工的HEV多蛋白前体,表明没有明显的病毒蛋白酶活性.
- 生物信息分析预测了HEV聚蛋白内的七个血栓分裂部位.
- 这些预测的分裂部位的突变性取消了复制系统中的病毒复制.
- 药理上抑制血清蛋白酶,包括血栓素,也可以防止HEV复制.
结论:
- 肝炎E病毒 (HEV) 聚蛋白加工主要由宿主细胞蛋白质酶,特别是血栓酶进行中介.
- 在聚蛋白成熟过程中,HEV复制依赖宿主血清蛋白酶.
- 病毒可能已经进化到依赖宿主机器,绕过对聚蛋白加工的病毒编码蛋白酶的需求.
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