中国科学家首次阐明埃博拉病毒入侵人体机制

2016-01-15 MedSci 新华社

2014年肆虐非洲的埃博拉疫情曾导致逾万人死亡。近日,中国科学家在埃博拉病毒研究中取得重大突破:中国科学院微生物研究所、中国疾病预防控制中心高福院士研究团队发现了一种新的病毒膜融合激发机制,从而在国际上率先阐明了埃博拉病毒是如何入侵人体的。这一成果15日在线发表在国际权威学术期刊《细胞》上。该研究为防控埃博拉疫情提供了重要理论基础,为抗病毒药物设计提供了新靶点。高福院士介绍,埃博拉、艾滋病、流感等

2014年肆虐非洲的埃博拉疫情曾导致逾万人死亡。近日,中国科学家在埃博拉病毒研究中取得重大突破:中国科学院微生物研究所、中国疾病预防控制中心高福院士研究团队发现了一种新的病毒膜融合激发机制,从而在国际上率先阐明了埃博拉病毒是如何入侵人体的。

这一成果15日在线发表在国际权威学术期刊《细胞》上。该研究为防控埃博拉疫情提供了重要理论基础,为抗病毒药物设计提供了新靶点。

高福院士介绍,埃博拉、艾滋病、流感等病毒都属于一类囊膜病毒,不能自己生长,必须进入人体细胞,利用人体细胞来产生子代病毒。“过去的研究发现,病毒入侵细胞时有4种膜融合激发机制。而我们发现埃博拉病毒的膜融合机制和已知的4种都不同,是新的第5种机制。”

埃博拉病毒如何感染人体?高福说,首先,埃博拉病毒粘附到宿主细胞的表面,然后宿主细胞发生了“坍塌”,形成了包裹着病毒的内吞体,进入到细胞内部。之后病毒膜与宿主细胞发生融合,就可以释放自身遗传物质,感染人体。

此前的研究发现,内吞体膜上的NPC1分子是埃博拉病毒入侵细胞的“通路”,但这条路如何走却一直是个未解之谜。高福研究组率先发现了其中的奥秘:原来NPC1分子有A、C、I三个腔内结构域。而埃博拉病毒在内吞体里经过一种酶的处理会“变身”,然后和C发生相互作用,病毒膜融合过程就会启动,从而发生病毒感染。高福等率先解析出了这个复合物的三维结构。

“打个比方,就好像我们把埃博拉病毒身上的一层伪装脱掉,发现它其实长得像一把锁,NPC1分子的腔内结构域C就好比一把钥匙,当钥匙插到锁里,就会启动病毒膜融合,继而发生病毒感染。”他说。

“这为抗病毒药物设计提供了新靶点。”高福说,“针对这种结合过程,科研人员就能够设计小分子或多肽抑制剂,把这个’锁眼’堵上,从而阻断埃博拉病毒的入侵过程。”




病毒与受体相互作用细节图

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