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Rabies

Rabies is a lethal zoonotic disease caused by a single-stranded, negative-sense RNA virus of the Lyssavirus genus, within the family Rhabdoviridae. Its primary mode of transmission to humans is through bites or saliva-contaminated scratches from infected mammals such as dogs, bats, raccoons, or foxes. Transmission can also occur if infectious saliva contacts abraded skin or intact mucous membranes, including the conjunctiva.Viral Entry and Early ReplicationOnce introduced at the bite or scratch...
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    科学领域:

    • 病毒学 病毒学
    • 结构生物学 结构生物学
    • 神经科学是一个神经科学.

    背景情况:

    • 阿尔法病毒是关节动物传播的重要人类病原体.
    • 东部马脑炎病毒 (EEEV) 是一种高度毒性的阿尔法病毒,会导致严重的神经病变.
    • EEEV和塞米利基森林病毒 (SFV) 使用大脑表达的非常低密度脂蛋白受体 (VLDLR) 和阿波利波蛋白E受体2 (ApoER2) 作为细胞进入受体.

    研究的目的:

    • 阐明EEEV和SFV与VLDLR结合的结构机制.
    • 了解进化上不同的阿尔法病毒如何利用相同的细胞受体.

    主要方法:

    • 使用单粒子冷电子显微镜 (cryo-EM) 进行了研究.
    • 确定了与VLDLR联结域复合的EEEV和SFV尖端糖蛋白的结构.

    主要成果:

    • EEEV通过其E2糖蛋白子单元上的基本残留物结合VLDLR.
    • SFV通过其E1糖蛋白上的两个基本残留物,一个独特的结合部位,参与VLDLR.
    • 这些结构显示了VLDLR上的EEEV和SFV的不同的绑定模式.

    结论:

    • 不同的阿尔法病毒采用不同的分子策略与相同的细胞受体相互作用.
    • 灵活的结合模式和与LDLR相关蛋白的小相互作用足迹有助于它们被各种病毒采用为受体.
    • 这种适应性表明,病毒获得LDLR家族蛋白质作为细胞受体的进化障碍很低.