An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors.

An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors.
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DOI:
10.1016/j.chom.2016.05.004
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发表时间:
2016-06-08
影响因子:
30.3
通讯作者:
Shi PY
Shi PY
中科院分区:
医学1区
文献类型:
--
作者:
Shan C;Xie X;Muruato AE;Rossi SL;Roundy CM;Azar SR;Yang Y;Tesh RB;Bourne N;Barrett AD;Vasilakis N;Weaver SC;Shi PY

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寨卡病毒(ZIKV)的亚洲血统最近引起流行病和严重疾病。解开导致病毒传播性和疾病严重程度增加的机制需要实验系统。我们报告了ZIKV的感染性cDNA克隆,其使用亚洲谱系的临床分离株产生。cDNA克隆衍生的RNA在细胞中具有感染性,产生重组ZIKV。重组病毒在已建立的ZIKV小鼠模型中是有毒的,导致与人类疾病相关的神经学体征。此外,重组ZIKV对埃及伊蚊具有感染性,因此提供了检查病毒传播的手段。感染性cDNA克隆进一步用于产生荧光素酶ZIKV,其表现出对泛黄病毒抑制剂的敏感性,突出了其用于抗病毒筛选的潜在效用。这种ZIKV反向遗传系统与小鼠和蚊子感染模型一起,可能有助于确定人类毒力和蚊子传播的病毒决定因素,并为疫苗和治疗策略提供信息。寨卡病毒(ZIKV)是寨卡病毒的一种。Shan等人产生了寨卡病毒的感染性cDNA克隆以及荧光素酶报告病毒。重组ZIKV在小鼠中是有毒的,在埃及伊蚊中是传染性的,因此可以帮助鉴定毒力和传播的病毒决定因素。
The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a pan-flavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission, as well as inform vaccine and therapeutic strategies. Zika virus (ZIKV) is causing devastating epidemics with severe disease. Shan et al. generated an infectious cDNA clone of Zika virus as well as a luciferase reporter virus. Recombinant ZIKV is virulent in mice and infectious in Aedes aegypti and thus may help identify viral determinants of virulence and transmission.
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期刊: Science (New York, N.Y.)
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