Dissecting the peptide motifs controlling coronavirus infections

剖析控制冠状病毒感染的肽基序

• 批准号: 10648391
• 负责人: Thomas Miller Gallagher
• 金额: $ 22.23万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10648391
• 关键词: Affect; Antiviral Agents; Binding; Biochemical; COVID-19 vaccine; Cell membrane; Cell surface; Cells; Cellular Structures; Coat Protein Complex I; Code; Communication; Complex; Coronavirus; Coronavirus Infections; Cytoplasm; Cytoplasmic Tail; Data; E protein; Endoplasmic Reticulum; Endosomes; Foundations; Goals; Human; Infection; Integration Host Factors; Knowledge; Laboratories; Membrane; Membrane Proteins; Methods; Molecular Chaperones; Mus; Organelles; Pathogenicity; Pathway interactions; Peptides; Process; Proteins; Recombinants; Recycling; Research; Site; System; Vesicle; Viral; Viral Matrix Proteins; Viral Proteins; Virion; Virus; Virus Diseases; Virus-like particle; comparative; improved; intracellular protein transport; knockout gene; novel coronavirus; particle; pharmacologic; protein transport; recombinant virus; sorting nexins; trafficking; vesicle transport; virus host interaction

PROJECT SUMMARY/ABSTRACT This proposal aims to evaluate coronavirus assembly and egress. These late infection stages are understudied relative to coronavirus entry replication. Additional research is necessary to reveal how host cell machineries facilitate assembly and egress. Therefore, this proposal specifically focuses on coronavirus membrane proteins, their interactions with host cell components, and the relevance of these contacts to efficient virion formation and emergence from infected cells. Guided by biochemical and protein structural data documenting interfaces between viral peptide motifs and host coatomer and retromer complexes, we will construct recombinant murine coronaviruses and corona virus‐like particles with alternative motifs. Comparisons of recombinant virus infections, along with reductionist approaches assessing the formation and subcellular transport of virus‐like particles, will reveal how coatomer and retromer‐sorting nexins operate in controlling viral membrane protein trafficking, virus particle formation, and particle egress pathways. By expanding the studies to human pathogenic coronaviruses, we expect to identify commonly utilized host machineries that might be targeted by antiviral therapeutics.

项目总结/摘要 该提案旨在评估冠状病毒的组装和流出。这些晚期感染阶段是 相对于冠状病毒进入复制研究不足。需要进行更多的研究， 揭示了宿主细胞机制如何促进组装和出口。因此，这项建议 特别关注冠状病毒膜蛋白，它们与宿主细胞的相互作用， 组分，以及这些接触与有效病毒体形成和出现的相关性 感染的细胞。以生物化学和蛋白质结构数据为指导，记录接口 在病毒肽基序和宿主外壳体和逆转录体复合物之间，我们将构建 重组鼠冠状病毒和具有替代基序的冠状病毒样颗粒。 重组病毒感染的比较，沿着与还原主义的方法评估， 病毒样颗粒的形成和亚细胞运输，将揭示如何coatomer和 逆转录分选连接蛋白在控制病毒膜蛋白运输、病毒颗粒 形成和粒子出口路径。通过将研究扩展到人类致病性 冠状病毒，我们希望确定常用的主机，可能是 被抗病毒治疗剂靶向。