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东部马类脑炎病毒E2葡萄糖蛋白协调甲酸和蛋白质受体依赖感染的三个负电荷的结合位点
Maria D H Alcorn1, Chengqun Sun1, Theron C Gilliland1
1Department of Immunology and Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261.
bioRxiv : the preprint server for biology
|November 22, 2024
概括
东部马脑炎病毒 (EEEV) 使用其E2糖蛋白上的多个位点来结合硫酸肝素 (HS) 和蛋白质受体,影响神经病毒性和传染性. 了解这些相互作用是控制EEEV传播和疾病的关键.
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:
- 东部马类脑炎病毒 (EEEV) 神经毒性与肝硫酸盐 (HS) 受体结合有关.
- 在E2糖蛋白上有三个带正电荷的氨基酸集群与EEEV-HS相互作用有关.
- 此外,EEEV还利用像VLDLR,ApoER2和LDLR这样的蛋白质受体.
研究的目的:
- 调查每个HS相互作用部位对EEEV感染的个人贡献.
- 确定这些部位在HS和蛋白质受体依赖感染中的作用 *in vitro*.
- 在动物模型中评估对EEEV复制的影响.
主要方法:
- 在EEEV E2糖蛋白氨基酸集群的位点定向突变发生.
- 使用表达HS和蛋白质受体的细胞进行*体外*感染测定.
- 在小鼠中进行动物研究以评估EEEV复制和疾病表型.
- 蚊子感染性测定. 蚊子感染性测定.
主要成果:
- 每个已识别的HS相互作用部位都对EEEV-HS和EEEV-蛋白受体结合有所贡献.
- 改变这些相互作用部位会影响小鼠中的EEEV疾病表型.
- 对这些部位的修改可以消除蚊子中的EEEV传染性.
结论:
- 在EEEV E2糖蛋白上存在多个HS结合位.
- 这些HS结合部位在功能上与蛋白质受体相互作用部位重叠.
- 这两种HS和蛋白质受体相互作用对于EEEV组织感染性和疾病致病性至关重要.
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