由ASFV pE146L诱导的ER重塑对于病毒复制至关重要
Yilin Guo1,2, Sai Niu1,2, Xueying Wang1,2
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Journal of virology
|August 6, 2025
概括
非洲猪瘟病毒 (ASFV) 内膜蛋白pE146L对于病毒复制至关重要. 破坏其结构或脂质结合功能会阻碍ASFV的组装,并为抗病毒药物开发提供一个新的目标.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 非洲猪瘟病毒 (ASFV) 在猪中引起严重的出血性疾病,影响全球猪业.
- 许多ASFV近200个编码蛋白质的功能仍然未被描述,这限制了我们对病毒复制的理解.
- 对ASFV复制和组装机制的有限知识阻碍了有效疫苗和抗病毒药物的开发.
研究的目的:
- 识别和描述非特征化的ASFV内膜蛋白pE146L.L.的功能.
- 阐明pE146L的结构和功能性质,包括它在病毒复制和与宿主细胞组件相互作用中的作用.
- 探索pE146L作为开发针对ASFV的新型抗病毒疗法的潜在目标.
主要方法:
- 对ASFV pE146L蛋白的鉴定和功能分析.
- 在受感染细胞内的局部化研究,包括内质网膜 (ER) 局部化和ER聚合的诱导.
- 对pE146L细胞外可溶性区域 (pE146L-ΔTM) 的高分辨率晶体结构确定.
- 生物化学分析,包括破坏二硫化键 (C103A突变) 和脂质结合测定.
主要成果:
- 内部包膜蛋白pE146L对于ASFV复制是必不可少的.
- pE146L局限于内分泌网膜光层,并诱导周核ER聚合,这对于病毒工厂的形成至关重要.
- pE146L-ΔTM的晶体结构揭示了它的二维性质,并且分子间二硫化物键的破坏取消了ER聚合和病毒复制.
- 通过带有正电荷的表面贴片,pE146L具有脂质结合能力,这表明它在脂质调节中的作用对ASFV复制至关重要.
结论:
- ASFV pE146L是一种多功能蛋白质,对病毒形态生成和复制至关重要.
- pE146L二极体的结构完整性及其脂质结合活性对其功能至关重要.
- 对于抗ASFV药物的开发来说,pE146L是一个有前途的新目标.
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