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TitleStructure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 436, Year 2018
Publish dateJan 30, 2018
AuthorsTibor Füzik / Petra Formanová / Daniel Růžek / Kentaro Yoshii / Matthias Niedrig / Pavel Plevka /
PubMed AbstractTick-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. ...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.
External linksNat Commun / PubMed:29382836 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 19.2 Å
Structure data

3752

5o6a

EMDB-3752, PDB-5o6a:
The cryo-EM structure of Tick-borne encephalitis virus mature particle
Method: EM (single particle) / Resolution: 3.9 Å

3754

5o6v

EMDB-3754, PDB-5o6v:
The cryo-EM structure of Tick-borne encephalitis virus complexed with Fab fragment of neutralizing antibody 19/1786
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-3755:
Cryo-EM map of Tick-borne encephalitis virus complexed with Fab fragment of neutralizing antibody 19/1786 at pH 5.8
Method: EM (single particle) / Resolution: 19.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • TBEV (virus)
  • mus musculus (house mouse)
  • tick-borne encephalitis virus (strain hypr)
  • House mouse (house mouse)
KeywordsVIRUS / tick-borne encephalitis virus / mature particle / cryo-EM / Fab 19/1786

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