低密度脂蛋白受体促进了多个脑性α病毒的感染
Hongming Ma1, Lucas J Adams2, Saravanan Raju1,2
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nature communications
|January 3, 2024
概括
低密度脂蛋白受体 (LDLR) 作为阿尔法病毒的进入因子,如东方马类脑炎病毒 (EEEV). 针对LDLR的可溶性诱蛋白显示出抑制阿尔法病毒感染的潜力.
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:
- 阿尔法病毒利用细胞受体进入,LDLR家族成员之前已被确定.
- 通过阻断已知的受体,无法完全抑制阿尔法病毒感染,这表明涉及其他因素.
研究的目的:
- 使用全基因组屏幕识别alphavirus的新型细胞进入因子.
- 描述已确定受体在阿尔法病毒结合和感染中的作用.
主要方法:
- 在小鼠神经元细胞中,CRISPR-Cas9全基因组功能丧失屏幕使用了嵌合式alphavirus.
- 候选受体的表达分析和结合研究.
- 开发和测试可溶性诱蛋白.
主要成果:
- 低密度脂蛋白受体 (LDLR) 被确定为阿尔法病毒的新进入因素.
- LDLR促进了东部马类脑炎病毒 (EEEV),西部马类脑炎病毒和Semliki森林病毒的结合和感染.
- 观察到LDLR的LA域3 (LA3) 和α病毒之间的低亲和相互作用,这可以通过LA3重复增强.
结论:
- LDLR作为多个α病毒的低亲和度受体.
- 向LDLR的可溶性诱蛋白在体外和体内表现出抑制alphavirus感染的有效性.
- 这项研究为缓解阿尔法病毒感染和相关疾病提供了潜在的治疗策略.
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