Füzik Tibor, Formanová Petra, Růžek Daniel, Yoshii Kentaro, Niedrig Matthias, Plevka Pavel
Structural Virology, Central European Institute of Technology, Masaryk University, Kamenice 753/5, 62500, Brno, Czech Republic.
Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic.
Nat Commun. 2018 Jan 30;9(1):436. doi: 10.1038/s41467-018-02882-0.
Tick-borne encephalitis virus (TBEV) causes 13,000 cases of human meningitis and encephalitis annually. However, the structure of the TBEV virion and its interactions with antibodies are unknown. Here, we present cryo-EM structures of the native TBEV virion and its complex with Fab fragments of neutralizing antibody 19/1786. Flavivirus genome delivery depends on membrane fusion that is triggered at low pH. The virion structure indicates that the repulsive interactions of histidine side chains, which become protonated at low pH, may contribute to the disruption of heterotetramers of the TBEV envelope and membrane proteins and induce detachment of the envelope protein ectodomains from the virus membrane. The Fab fragments bind to 120 out of the 180 envelope glycoproteins of the TBEV virion. Unlike most of the previously studied flavivirus-neutralizing antibodies, the Fab fragments do not lock the E-proteins in the native-like arrangement, but interfere with the process of virus-induced membrane fusion.
蜱传脑炎病毒（TBEV）每年导致13000例人类脑膜炎和脑炎病例。然而，TBEV病毒粒子的结构及其与抗体的相互作用尚不清楚。在此，我们展示了天然TBEV病毒粒子及其与中和抗体19/1786的Fab片段复合物的冷冻电镜结构。黄病毒基因组的传递依赖于在低pH值下触发的膜融合。病毒粒子结构表明，在低pH值下质子化的组氨酸侧链的排斥相互作用可能有助于破坏TBEV包膜和膜蛋白的异源四聚体，并诱导包膜蛋白胞外结构域从病毒膜上脱离。Fab片段与TBEV病毒粒子180个包膜糖蛋白中的120个结合。与大多数先前研究的黄病毒中和抗体不同，Fab片段不会将E蛋白锁定在类似天然的排列中，而是干扰病毒诱导的膜融合过程。
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