Abstract

The main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype. A 3.8 Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows a high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for the design of novel vaccines against diseases caused by flaviviruses.

Details

Title
Structural diversity of tick-borne encephalitis virus particles in the inactivated vaccine based on strain Sofjin
Author
Moiseenko, Andrey 1   VIAFID ORCID Logo  ; Zhang, Yichen 2   VIAFID ORCID Logo  ; Vorovitch, Mikhail F 3 ; Ivanova, Alla L 4 ; Liu, Zheng 5   VIAFID ORCID Logo  ; Osolodkin, Dmitry I 3   VIAFID ORCID Logo  ; Egorov, Alexey M 6 ; Ishmukhametov, Aydar A 3   VIAFID ORCID Logo  ; Sokolova, Olga S 7   VIAFID ORCID Logo 

1  Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia 
2  Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, People’s Republic of China 
3  FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow, Russia; Sechenov First Moscow State Medical University, Moscow, Russia 
4  FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow, Russia 
5  Kobilka Institute of Innovative Drug Discovery, School of Medicine, Chinese University of Hong Kong, Shenzhen, People’s Republic of China 
6  FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow, Russia; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia 
7  Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia; Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, People’s Republic of China 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2023.2290833
ProQuest document ID
3142112061
Copyright
© 2024 FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.