PNAS :科学家发现寨卡病毒突变增加传播和感染

2020-08-10 酶美 BioArt

寨卡病毒是一种蚊媒黄病毒,1947年首次在非洲乌干达发现。2007年以前,寨卡病毒在非洲和亚洲部分地区传播,但是并没有导致严重疾病和大范围暴发,只有零星寨卡病毒感染病例。

寨卡病毒是一种蚊媒黄病毒,1947年首次在非洲乌干达发现。2007年以前,寨卡病毒在非洲和亚洲部分地区传播,但是并没有导致严重疾病和大范围暴发,只有零星寨卡病毒感染病例。寨卡病毒在进化中分为非洲株系和亚洲株系,寨卡病毒亚洲株系在2007年在西太平洋密克罗尼西亚亚帕岛暴发,随后在2013年传播到法属波利尼西亚和其他南太平洋岛屿,并在2015年到达美洲,并迅速扩散到40多个国家,造成大规模疫情。寨卡病毒引起的严重疾病包括格林巴利综合症和新生儿小头症。

2020年8月, PNAS在线发表了单超研究员与德克萨斯大学医学部史佩勇教授联合研究的最新成果,论文题为A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission。研究表明了2015年寨卡病毒衣膜突变是感染传播增强的原因之一。

在这项研究中,研究人员将2015流行株与2010年的毒株进行了分子进化比较,并确定了整个基因组中的7个氨基酸位点变化。并利用反向遗传学系统对7个位点在2010年的毒株中进行了验证。神经毒力结果显示,其中3个突变体在初生小鼠中产生的死亡率高于2010年的毒株,而衣壳蛋白E-V473M突变产生的死亡率曲线与2015流行菌株相同。

由于寨卡病毒感染的可以引起母婴传播和小头症,因此该研究小组还利用接近自然感染途径在孕鼠模型中验证了E-V473M对母婴传播的影响。数据显示,E-V473M突变体在胎盘和胎脑中的病毒载量明显高于对照2010年的毒株,这表明E-V473M增强了孕期母婴传播的可能性,进一步可能导致新生儿小头症的出现。

为了确定E-V473M是否可以通过增强人类病毒血症来增强寨卡病毒的传播,从而导致蚊媒更有效地获得病毒而引起感染。小鼠实验显示,该突变体可以更快地引起病毒血症。研究小组还使用竞争适应性方法,在灵长类动物中验证了突变对病毒血症的影响。该实验结果表明,突变体E-V473M在蚊虫体内的比例高于2010年的毒株,提示了突变可能通过增强在灵长类动物模型中适应性,进一步地提高了蚊虫获得病毒的能力,从而为寨卡病毒流行提供了帮助。

该论文为中科院武汉病毒所与德克萨斯大学医学部联合研究,单超研究员为论文的共同第一作者和通讯作者,德克萨斯大学医学部的夏鸿杰博士为共同第一作者,史佩勇教授和Scott Weaver 教授为共同通讯作者。

原始出处:

Chao Shan, Hongjie Xia, Sherry L Haller, et al.A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.Proc Natl Acad Sci U S A. 2020 Aug 3;202005722. doi: 10.1073/pnas.2005722117.

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    2020-10-29 drwjr
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