Faculty of Biological and Environmental Sciences, Molecular and Integrative Bioscience Research Programme, University of Helsinki, Helsinki, Finland.
Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Sci Adv. 2024 Jul 5;10(27):eadl1888. doi: 10.1126/sciadv.adl1888. Epub 2024 Jul 3.
We present structures of three immature tick-borne encephalitis virus (TBEV) isolates. Our atomic models of the major viral components, the E and prM proteins, indicate that the pr domains of prM have a critical role in holding the heterohexameric prM3E3 spikes in a metastable conformation. Destabilization of the prM furin-sensitive loop at acidic pH facilitates its processing. The prM topology and domain assignment in TBEV is similar to the mosquito-borne Binjari virus, but is in contrast to other immature flavivirus models. These results support that prM cleavage, the collapse of E protein ectodomains onto the virion surface, the large movement of the membrane domains of both E and M, and the release of the pr fragment from the particle render the virus mature and infectious. Our work favors the collapse model of flavivirus maturation warranting further studies of immature flaviviruses to determine the sequence of events and mechanistic details driving flavivirus maturation.
我们展示了三种不成熟的蜱传脑炎病毒（TBEV）分离株的结构。我们主要病毒成分 E 和 prM 蛋白的原子模型表明，prM 的 pr 结构域在将异六聚体 prM3E3 刺突保持在亚稳定构象中起着关键作用。在酸性 pH 下，prM 弗林敏感环的失稳促进了其加工。TBEV 中的 prM 拓扑结构和结构域分配与蚊媒 Binjari 病毒相似，但与其他不成熟的黄病毒模型相反。这些结果支持 prM 切割、E 蛋白外域在病毒表面上的坍塌、E 和 M 的膜结构域的大运动以及 pr 片段从颗粒中的释放使病毒成熟并具有感染性。我们的工作支持黄病毒成熟的坍塌模型，需要进一步研究不成熟的黄病毒，以确定驱动黄病毒成熟的事件顺序和机制细节。
