Picornavirus Genome Replication

小核糖核酸病毒基因组复制

• 批准号: 10447359
• 负责人: CRAIG E. CAMERON
• 金额: $ 53.4万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10447359
• 关键词: Achievement; Anabolism; Biochemical; Biological Process; Categories; Cytoplasm; Development; Enterovirus; FOS gene; Family Picornaviridae; Genetic Transcription; Genome; Goals; Human poliovirus; Infection; Instruction; Mammalian Cell; Membrane; Phospholipids; Picornaviridae Infections; Public Health; RNA; RNA Viruses; Research; Translations; Vaccines; Virion; Virus; biophysical properties; falls; inhibitor; lipidome; membrane biogenesis; novel; posttranscriptional; trafficking

All positive-strand RNA viruses require host membranes for multiplication, even non-enveloped viruses like poliovirus (PV). In some cases, viruses simply hijack host membranes and use them intact. However, in other cases, viruses remodel the entire host lipidome to create virus-induced membranes with unique phospholipid composition, which, in turn, confers upon these membranes unique biochemical and biophysical properties to enable unique biological function. PV, related enteroviruses, and likely many other viruses, fall into this latter category. What is so astonishing about the PV-induced transformations is that they only require translation of the infecting RNA, without the need for genome replication or host transcription. What this circumstance suggests is that post-transcriptional and/or post-translational mechanisms exist in the mammalian cell cytoplasm capable of completely reprogramming phospholipid biosynthesis and membrane biogenesis in a matter of minutes and that one or a few master regulators, which can be coopted by PV, likely control these mechanisms. The overarching premise of the research proposed during the extension is that our studies will illuminate mechanisms regulating membrane biogenesis, function, and trafficking by understanding how PV hijacks and coopts these mechanisms. We will pursue the following specific aims: Aim 1 - Study contributions of 3CD to virion assembly, trafficking, and egress; Aim 2 – Coopting of c-Fos by PV to induce phospholipid biosynthesis and membrane biogenesis; and Aim 3 – Characterization of the dynamics, mechanisms, and functions of host-lipidome remodeling during PV infection. RELEVANCE (See instructions): Picornaviruses represent an existing and emerging threat to U.S. public health. Achievement of the goals of the application will provide novel targets and mechanisms for development of inhibitors to treat infections by picornaviruses, especially those for which vaccines are not available.

所有阳性RNA病毒都需要繁殖的宿主机制，甚至是非发育的病毒 脊髓灰质炎病毒（PV）。在某些情况下，病毒只是劫持了宿主机制，并完整地使用它们。但是，在 其他情况，病毒重塑了整个宿主脂质仪，以创建具有独特的病毒诱导的机制 磷脂成分，反过来供应这些膜独特的生化和 生物物理特性以实现独特的生物学功能。 PV，相关肠病毒，可能有很多 其他病毒，属于以后的类别。 PV引起的转换是如此惊人的是 他们只需要翻译感染的RNA，而无需基因组复制或宿主 转录。这种情况表明的是转录后和/或翻译后 机制存在于能够完全重新编程磷脂的哺乳动物细胞质中 生物合成和膜生物发生在几分钟内，一个或几个主调节剂， 可以通过PV来控制这些机制。研究的总体前提 在扩展期间提出的是，我们的研究将照亮调节膜的机制 通过了解PV如何劫持这些机制，生物发生，功能和运输。我们 将追求以下具体目标：目标1- 3CD对病毒座组件的研究贡献，贩运， 和出口； AIM 2 - 通过PV合作诱导磷脂生物合成和膜 生物发生； AIM 3 - 宿主 - 莱迪术的动力学，机制和功能的表征 光伏感染期间的重塑。 相关性（请参阅说明）： Picornaviruses代表了对美国公共卫生的现有和新兴威胁。实现目标 该应用将为开发抑制剂治疗感染的新目标和机制 通过PICORNAVIRES，尤其是那些无法提供疫苗的病毒。