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.

所有正链RNA病毒都需要宿主膜才能繁殖，即使是非包膜病毒，比如