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Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody

Author

Listed:
  • Tibor Füzik

    (Masaryk University)

  • Petra Formanová

    (Veterinary Research Institute)

  • Daniel Růžek

    (Veterinary Research Institute
    Biology Centre of the Czech Academy of Sciences)

  • Kentaro Yoshii

    (Hokkaido University)

  • Matthias Niedrig

    (Robert Koch Institute)

  • Pavel Plevka

    (Masaryk University)

Abstract

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.

Suggested Citation

  • Tibor Füzik & Petra Formanová & Daniel Růžek & Kentaro Yoshii & Matthias Niedrig & Pavel Plevka, 2018. "Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02882-0
    DOI: 10.1038/s41467-018-02882-0
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    Cited by:

    1. Xiaojing Chen & Fan Li & Qikai Yin & Wenjing Liu & Shihong Fu & Ying He & Wenwen Lei & Songtao Xu & Guodong Liang & Shiwen Wang & Guang Yang & Xiaopeng Qi & Huanyu Wang, 2019. "Epidemiology of tick-borne encephalitis in China, 2007- 2018," PLOS ONE, Public Library of Science, vol. 14(12), pages 1-11, December.

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