...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras
【24h】

Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras

机译：传染性基因型和基因型丙型肝炎病毒嵌合体的构建和鉴定

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Chronic liver disease caused by infection with hepatitis C virus (HCV) is an important global health problem that currently affects 170 million people. A major impediment in HCV research and drug development has been the lack of culture systems supporting virus production. This obstacle was recently overcome by using JFH1-based full-length genomes that allow production of viruses infectious both in vitro and in vivo. Although this improvement was important, because of the restriction to the JFH1 isolate and a single chimera consisting of J6CF and JFH1-derived sequences, broadly based comparative studies between different HCV strains were not possible. Therefore, in this study we created a series of further chimeric genomes allowing production of infectious genotype (GT) 1a, 1b, 2a, and 3a particles. With the exception of the GT3a/JFH1 chimera, efficient virus production was obtained when the genome fragments were fused via a site located right after the first transmembrane domain of NS2. The most efficient construct is a GT2a/2a chimera consisting of J6CF- and JFH1-derived sequences connected via this junction. This hybrid, designated Jc1, yielded infectious titers 100-to 1,000-fold higher than the parental isolate and all other chimeras, suggesting that determinants within the structural proteins govern kinetic and efficiency of virus assembly and release. Finally, we describe an E1-specific antiserum capable of neutralizing infectivity of all HCV chimeras.
机译：由丙型肝炎病毒（HCV）感染引起的慢性肝病是一个重要的全球健康问题，目前影响1.7亿人。 HCV研究和药物开发的主要障碍是缺乏支持病毒生产的培养系统。最近，通过使用基于JFH1的全长基因组克服了这一障碍，该基因组允许在体内和体外产生感染性病毒。尽管这一改进很重要，但由于对JFH1分离株的限制以及由J6CF和JFH1衍生的序列组成的单个嵌合体，因此不可能在不同HCV株之间进行广泛的比较研究。因此，在这项研究中，我们创建了一系列进一步的嵌合基因组，可产生传染性基因型（GT）1a，1b，2a和3a颗粒。除GT3a / JFH1嵌合体外，当基因组片段通过位于NS2的第一个跨膜结构域之后的位点融合时，可获得高效的病毒生产。最有效的构建体是GT2a / 2a嵌合体，该嵌合体由通过此连接点连接的J6CF和JFH1衍生序列组成。该杂种命名为Jc1，其感染效价比亲本分离株和所有其他嵌合体高100至1,000倍，表明结构蛋白内的决定簇决定着病毒装配和释放的动力学和效率。最后，我们描述了一种E1特异性抗血清，能够中和所有HCV嵌合体的感染性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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