Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Viruses. 2020 Dec 23;13(1):13. doi: 10.3390/v13010013.
Flaviviruses are a group of positive-sense RNA viruses that are primarily transmitted through arthropod vectors and are capable of causing a broad spectrum of diseases. Many of the flaviviruses that are pathogenic in humans are transmitted specifically through mosquito vectors. Over the past century, many mosquito-borne flavivirus infections have emerged and re-emerged, and are of global importance with hundreds of millions of infections occurring yearly. There is a need for novel, effective, and accessible vaccines and antivirals capable of inhibiting flavivirus infection and ameliorating disease. The development of therapeutics targeting viral entry has long been a goal of antiviral research, but most efforts are hindered by the lack of broad-spectrum potency or toxicities associated with on-target effects, since many host proteins necessary for viral entry are also essential for host cell biology. Mosquito-borne flaviviruses generally enter cells by clathrin-mediated endocytosis (CME), and recent studies suggest that a subset of these viruses can be internalized through a specialized form of CME that has additional dependencies distinct from canonical CME pathways, and antivirals targeting this pathway have been discovered. In this review, we discuss the role and contribution of endocytosis to mosquito-borne flavivirus entry as well as consider past and future efforts to target endocytosis for therapeutic interventions.
黄病毒是一组正链 RNA 病毒，主要通过节肢动物媒介传播，能够引起广泛的疾病。许多对人类致病的黄病毒都是通过蚊子媒介特异性传播的。在过去的一个世纪里，许多蚊媒传播的黄病毒感染已经出现并再次出现，具有全球性的重要性，每年有数亿人感染。因此需要新型、有效且易于获得的疫苗和抗病毒药物来抑制黄病毒感染并改善疾病。靶向病毒进入的治疗方法的开发一直是抗病毒研究的目标，但由于缺乏广谱效力或与靶点相关的毒性，大多数努力都受到了阻碍，因为许多病毒进入所需的宿主蛋白对宿主细胞生物学也是必不可少的。蚊媒传播的黄病毒通常通过网格蛋白介导的内吞作用（CME）进入细胞，最近的研究表明，其中一些病毒可以通过一种特殊形式的 CME 内化，这种 CME 具有与经典 CME 途径不同的额外依赖性，并且已经发现了针对该途径的抗病毒药物。在这篇综述中，我们讨论了内吞作用在蚊媒传播的黄病毒进入中的作用和贡献，并考虑了过去和未来针对内吞作用进行治疗干预的努力。
