多个阿尔法病毒使用LDLR作为细胞进入受体
Xiaofeng Zhai1, Xiaoling Li1, Michael Veit2
1Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Nature communications
|January 20, 2024
概括
低密度脂蛋白受体 (LDLR) 作为多个α病毒的细胞进入因子,包括盖塔病毒. 准LDLR连接体结合域可能会提供一种新的抗病毒策略来对抗这些重要的树冠病毒.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 阿尔法病毒是蚊子传播的树状病毒,对人类和牲畜构成重大公共卫生风险.
- 现有的已识别的受体不能完全解释在一些阿尔法病毒中观察到的广泛的宿主范围和组织热带性,如盖塔病毒 (GETV).
研究的目的:
- 为了确定参与阿尔法病毒进入的新型细胞受体.
- 调查低密度脂蛋白受体 (LDLR) 在GETV和其他α病毒的细胞进入中的作用.
主要方法:
- 细胞中LDLR的宫外表达.
- 通过LDLR调解的GETV结合和内部化的分析.
- 调查病毒E2-E1尖峰和LDLR联体结合域 (LBD) 之间的相互作用.
- 利用针对LBD和GST-LBD融合蛋白的抗体来抑制病毒感染.
- 在LDLR-LBD中,关键氨基酸的局部导向突变发生.
主要成果:
- 低密度脂蛋白受体 (LDLR) 被确定为GETV,塞米利基森林病毒 (SFV),罗斯河病毒 (RRV) 和贝巴鲁病毒 (BEBV) 的新型细胞进入因子.
- LDLR通过病毒E2-E1尖峰和LDLR连体结合域 (LBD) 之间的相互作用促进GETV细胞结合和内化.
- 对LBD和GST-LBD融合蛋白的抗体在体外和体内有效抑制了GETV感染.
- 在LDLR-LBD的CR4和CR5域内的特定突变显著减少了病毒进入的20倍以上.
结论:
- 低密度脂蛋白受体 (LDLR) 是多个阿尔法病毒的保存细胞进入因子.
- 阿尔法病毒E2-E1峰值和LDLR-LBD之间的相互作用对于病毒的进入至关重要.
- 向LDLR-LBD是一个有前途的治疗策略,用于开发针对一系列α病毒的抗病毒药物.
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