• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Journal of Virology >Chimeric tick-borne encephalitis and dengue type 4 viruses: effects of mutations on neurovirulence in mice.
【2h】

Chimeric tick-borne encephalitis and dengue type 4 viruses: effects of mutations on neurovirulence in mice.

机译：嵌合tick传脑炎和登革热4型病毒：突变对小鼠神经毒性的影响。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Two new chimeric flaviviruses were constructed from full-length cDNAs that contained tick-borne encephalitis virus (TBEV) CME or ME structural protein genes and the remaining genes derived from dengue type 4 virus (DEN4). Studies involving mice inoculated intracerebrally with the ME chimeric virus indicated that it retained the neurovirulence of its TBEV parent from which its pre-M and E genes were derived. However, unlike parental TBEV, the chimeric virus did not produce encephalitis when mice were inoculated peripherally, indicating a loss of neuroinvasiveness. In the present study, the ME chimeric virus (vME) was subjected to mutational analysis in an attempt to reduce or ablate neurovirulence measured by direct inoculation of virus into the brain. We identified three distinct mutations that were each associated independently with a significant reduction of mouse neurovirulence of vME. These mutations ablated (i) the TBEV pre-M cleavage site, (ii) the TBEV E glycosylation site, or (iii) the first DEN4 NS1 glycosylation site. In contrast, ablation of the second DEN4 NS1 glycosylation site or the TBE pre-M glycosylation site or amino acid substitution at two positions in the TBEV E protein increased neurovirulence. The only conserved feature of the three attenuated mutants was restriction of virus yield in both simian and mosquito cells. Following parenteral inoculation, these attenuated mutants induced complete resistance in mice to fatal encephalitis caused by the highly neurovirulent vME.
机译：从全长cDNA构建了两种新的嵌合黄病毒，其中含有tick传脑炎病毒（TBEV）CME或ME结构蛋白基因，其余基因均来自登革热4型病毒（DEN4）。涉及在脑内接种ME嵌合病毒的小鼠的研究表明，它保留了其TBEV亲本的神经毒力，其前M和E基因是由其产生的。但是，与父母的TBEV不同，当小鼠外周接种时，嵌合病毒不会产生脑炎，表明神经侵袭力丧失。在本研究中，对ME嵌合病毒（vME）进行了突变分析，以尝试通过直接将病毒接种到大脑中来减少或消除神经毒力。我们确定了三个不同的突变，每个突变与vME的小鼠神经毒力的显着降低独立相关。这些突变消除了（i）TBEV M前切割位点，（ii）TBEV E糖基化位点，或（iii）第一个DEN4 NS1糖基化位点。相反，第二个DEN4 NS1糖基化位点或TBE pre-M糖基化位点的消融或TBEV E蛋白中两个位置的氨基酸取代增加了神经毒性。这三个减毒突变体的唯一保守特征是在猿猴和蚊子细胞中都限制了病毒产量。肠胃外接种后，这些减毒突变体在小鼠中诱导了对高度神经毒性vME引起的致命性脑炎的完全抵抗。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号