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

FÜZIK, Tibor, P. FORMANOVA, D. RUZEK, K. YOSHII, M. NIEDRIG and Pavel PLEVKA. Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody. Nature Communications. London: Nature Publishing Group, 2018, vol. 9, JAN, p. 436-446. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-018-02882-0.

Basic information

• Original name: Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody
• Authors: FÜZIK, Tibor (703 Slovakia, belonging to the institution), P. FORMANOVA (203 Czech Republic), D. RUZEK (203 Czech Republic), K. YOSHII (392 Japan), M. NIEDRIG (276 Germany) and Pavel PLEVKA (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Nature Communications, London, Nature Publishing Group, 2018, 2041-1723.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10607 Virology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 11.878
• RIV identification code: RIV/00216224:14740/18:00101775
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41467-018-02882-0
• UT WoS: 000423510600013
• Keywords in English: WEST-NILE-VIRUS; DENGUE VIRUS; MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; ELECTRON-MICROSCOPY; ZIKA VIRUS; CELL ENTRY; ACIDIC PH; MATURATION; PROTEINS
• Tags: CF CRYO, CF PROT, rivok
• Tags: International impact, Reviewed

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.

Links

• GA17-02196S, research and development project: Name: Strukturní studie flavivirů a mechanismu jejich neutralizace protilátkami

Investor: Czech Science Foundation, Structural studies of flaviviruses and their neutralization by antibodies

• LM2015043, research and development project: Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

• LM2015085, research and development project: Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

• LQ1601, research and development project: Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

• 3041, interní kód MU: Name: Structural studies of human and animal pathogens from the order Picornavirales

Investor: EMBO (European Molecular Biology Organization)

• 335855, interní kód MU: Name: Structural studies of human picornaviruses directed towards development of anti-viral compounds (Acronym: PicoDrugs)

Investor: European Union, Ideas