乙型肝炎病毒前基因组RNA中的G-quadruplex促进其翻译
Jingjing Wang1, Haiyan Huang2, Kaitao Zhao1
1State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, China.
The Journal of biological chemistry
|August 11, 2023
概括
乙型肝炎病毒 (HBV) 前基因组RNA (pgRNA) 含有G-四重复 (G4) 结构. 这种G4结构对于调节病毒mRNA翻译和增加核心蛋白水平至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 乙型肝炎病毒 (HBV) 具有紧的基因组,需要有效的病毒生命周期机制.
- 越来越多地认识到G-四重复 (G4) 结构在病毒生命周期中的调节作用.
- 在复制过程中,HBV基因组内的G4结构的特定功能仍然不清楚.
研究的目的:
- 为了研究G-quadruplex (G4) 结构在B型肝炎病毒 (HBV) 复制中的作用.
- 阐明G4结构影响HBV病毒蛋白表达的机制.
主要方法:
- 用G4稳定剂pyridostatin (PDS) 治疗HBV复制能力和感染细胞.
- 对病毒RNA (pcRNA,pgRNA) 和蛋白质 (HBeAg,HBc) 水平的分析.
- 在体外翻译测试使用合成的HBVRNAs.
- 生物信息分析和CD光谱学用于识别和描述G4结构.
- 局部定向突变发生,以破坏pgRNA中的G4结构.
主要成果:
- 皮里多斯塔丁 (PDS) 治疗增加了乙型肝炎病毒核心蛋白 (HBc) 水平和HBeAg ELISA读数,但不是病毒RNA水平,表明转录后调节.
- PDS从基因组前RNA (pgRNA) 特别增强了HBc表达,而不是从先前RNA (pcRNA) 获得的HBeAg.
- 生物信息学分析和CD光谱学证实了HBVpgRNA中保存的G4结构.
- 在pgRNA中G4结构的破坏取消了PDS反应,并在体外降低了HBc水平.
结论:
- 乙型肝炎病毒 (HBV) 前基因组RNA (pgRNA) 含有功能G-四重复 (G4) 结构.
- 这种G4结构在调节病毒mRNA的翻译方面发挥着关键作用,特别是增强核心蛋白 (HBc) 表达.
- 准病毒G4结构代表了控制HBV复制的潜在策略.
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