Unravelling Tick-Borne Encephalitis Virus Neutralisation Mechanisms with Cryo-EM

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F23%3A00134306" target="_blank" >RIV/00216224:14740/23:00134306 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.imp.ac.at/research/cryo-em-symposium" target="_blank" >https://www.imp.ac.at/research/cryo-em-symposium</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Unravelling Tick-Borne Encephalitis Virus Neutralisation Mechanisms with Cryo-EM

Popis výsledku v původním jazyce

Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a severe disease that can lead to fatal central nervous system inflammation. Despite the availability of vaccines, vaccination rates in the most affected areas, such as the Czech Republic, are low. With TBE cases on the rise, the need for targeted treatments is growing. Antibodies have shown promise in a mouse model, where intravenous administration of TBEV-specific antibodies served as a treatment. However, our understanding of the molecular mechanisms behind TBEV neutralisation remains limited.To address this gap, we investigated the interactions between the TBEV Neudörfl strain and two neutralising mouse monoclonal antibodies, IC3 and A4, which bind to distinct domains of the TBEV envelope protein. We purified TBEV from infected tissue culture cells, mixed it with Fab fragments derived from the neutralising antibodies, and vitrified the samples on grids for cryo-electron microscopy. Using single-particle analysis, we solved the structures of the TBEV-Fab complexes from the collected micrographs.By deciphering the molecular basis of TBEV neutralisation by antibodies, we aim to gain insights into the significance of different epitopes on the viral surface. This knowledge may pave the way for the tailored design of therapeutic antibodies or more specific vaccines in the future.

Název v anglickém jazyce

Unravelling Tick-Borne Encephalitis Virus Neutralisation Mechanisms with Cryo-EM

Popis výsledku anglicky

Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a severe disease that can lead to fatal central nervous system inflammation. Despite the availability of vaccines, vaccination rates in the most affected areas, such as the Czech Republic, are low. With TBE cases on the rise, the need for targeted treatments is growing. Antibodies have shown promise in a mouse model, where intravenous administration of TBEV-specific antibodies served as a treatment. However, our understanding of the molecular mechanisms behind TBEV neutralisation remains limited.To address this gap, we investigated the interactions between the TBEV Neudörfl strain and two neutralising mouse monoclonal antibodies, IC3 and A4, which bind to distinct domains of the TBEV envelope protein. We purified TBEV from infected tissue culture cells, mixed it with Fab fragments derived from the neutralising antibodies, and vitrified the samples on grids for cryo-electron microscopy. Using single-particle analysis, we solved the structures of the TBEV-Fab complexes from the collected micrographs.By deciphering the molecular basis of TBEV neutralisation by antibodies, we aim to gain insights into the significance of different epitopes on the viral surface. This knowledge may pave the way for the tailored design of therapeutic antibodies or more specific vaccines in the future.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/GX19-25982X" target="_blank" >GX19-25982X: Analýza replikace enterovirů s využitím elektronové mikroskopie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů