Dissecting the peptide motifs controlling coronavirus infections

项目摘要/摘要 这项建议旨在评估冠状病毒的组装和出口。这些晚期感染阶段是 关于冠状病毒入口复制的研究不足。有必要进行额外的研究，以 揭示宿主细胞机器如何促进组装和出口。因此，这项提议 特别关注冠状病毒膜蛋白及其与宿主细胞的相互作用 成分，以及这些接触与有效病毒粒子形成和出现的相关性 从受感染的细胞中。以生化和蛋白质结构数据为指导，记录接口 在病毒多肽基序和宿主共聚物和逆转录复合体之间，我们将构建 重组小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，以及简化论方法评估 病毒样颗粒的形成和亚细胞运输，将揭示Cotom和 逆转录-分选连接素在控制病毒膜蛋白运输、病毒颗粒 形成和粒子逃逸路径。通过将研究扩展到人类致病 冠状病毒，我们希望确定常用的宿主机器可能是 是抗病毒治疗药物的靶点。

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.