• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Dissecting the Multifunctional Arenavirus Nucleoprotein.
【24h】

Dissecting the Multifunctional Arenavirus Nucleoprotein.

机译：解剖多功能脊椎病毒核蛋白。

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

Several arenaviruses cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. Arenavirus nucleoprotein (NP), the most abundant viral protein in infected cells and virions, encapsidates the viral genomic RNA, and this NP-RNA complex, together with the viral L polymerase, forms the viral ribonucleoprotein (vRNP) complex that directs vRNA replication and gene transcription. Generation of infectious arenavirus progeny requires packaging of these vRNPs into budding particles, a process in which the arenavirus matrix-like protein (Z) plays a central role. In this work, we document the self-association (homotypic interaction) of NP from the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), as well as those of the hemorrhagic fever arenaviruses Lassa virus (LASV) and Machupo virus (MACV). We also show heterotypic interaction between NPs from both closely (LCMV and LASV) and distantly (LCMV and MACV) genetically-related arenaviruses. LCMV-NP self-association is dependent on the presence of single-stranded RNA and mediated by the N-terminal region of the NP. We also describe the ability and the domain of LCMV-NP required for the interaction with the Z protein, demonstrating that this domain overlap with a previously documented C-terminal region that counteracts the host type I interferon (IFN-I) response. However, single amino acid mutations affecting the anti-IFN-I function of LCMV-NP did not disrupt the NP-Z interaction, suggesting that within the C-terminal region of NP, different amino acid residues contribute to these two distinct and segregable NP functions. Similarly, we confirm this NP-Z interaction for the HF arenavirus Lassa virus (LASV). Exhaustive analysis in LCMV-NP by the generation of single amino acid mutants demonstrated the important role of the residue D471 in its self-association. Substitutions at this position abrogate NP oligomerization, affecting its ability to replicate and transcribe a Minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to double-stranded (ds)RNA analogs was retained. Additionally, we also document the dominant negative effect of the D471G mutation on viral infection. These results demonstrate that the NP-NP and NP-Z interactions are great potential target for the development of antiviral drugs to combat human-pathogenic arenaviruses.
机译：几种沙粒病毒会导致人类出血热（HF）疾病，与高发病率和高死亡率相关。甲状旁腺病毒核蛋白（NP）是被感染的细胞和病毒粒子中最丰富的病毒蛋白，衣壳化了病毒基因组RNA，该NP-RNA复合物与病毒L聚合酶一起形成了病毒核糖核蛋白（vRNP）复合物，可指导vRNA复制和基因转录。感染性腔病毒的后代的产生需要将这些vRNP包装成萌芽的颗粒，在此过程中，腔病毒的基质样蛋白（Z）发挥着核心作用。在这项工作中，我们记录了原型鼻腔病毒淋巴性脉络膜脑膜炎病毒（LCMV）以及出血热鼻腔病毒拉萨病毒（LASV）和马丘波病毒（MACV）的NP的自我关联（同质相互作用）。我们还显示了近距离（LCMV和LASV）和远距离（LCMV和MACV）遗传相关的鼻病毒之间NP之间的异型相互作用。 LCMV-NP的自缔合依赖于单链RNA的存在并由NP的N末端区域介导。我们还描述了与Z蛋白相互作用所需的LCMV-NP的能力和结构域，证明了该结构域与抵消宿主I型干扰素（IFN-I）应答的先前记录的C端区域重叠。但是，影响LCMV-NP的抗IFN-I功能的单个氨基酸突变不会破坏NP-Z相互作用，这表明在NP的C端区域内，不同的氨基酸残基有助于这两个不同且可分离的NP功能。同样，我们确认了HF沙粒病毒拉萨病毒（LASV）的这种NP-Z相互作用。在LCMV-NP中通过单个氨基酸突变体的产生进行的详尽分析表明，残基D471在其自缔合中具有重要作用。在此位置的取代取消了NP寡聚，影响了其复制和转录Minigenome报告质粒的能力。但是，它具有与Z蛋白相互作用，抵消细胞干扰素应答并与双链（ds）RNA类似物结合的能力。此外，我们还记录了D471G突变对病毒感染的显性负作用。这些结果表明，NP-NP和NP-Z相互作用是开发抗病毒药物对抗人类致病性鼻病毒的巨大潜在目标。

著录项

  • 作者

    Ortiz Riano, Emilio.;

  • 作者单位

    University of Rochester.;

  • 授予单位 University of Rochester.;
  • 学科 Biology Virology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 148 p.
  • 总页数 148
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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