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Molecular Organisation of Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species publi...

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Autores principales: Pulkkinen, Lauri I. A., Barrass, Sarah V., Domanska, Aušra, Överby, Anna K., Anastasina, Maria, Butcher, Sarah J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027435/
https://www.ncbi.nlm.nih.gov/pubmed/35458522
http://dx.doi.org/10.3390/v14040792
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author Pulkkinen, Lauri I. A.
Barrass, Sarah V.
Domanska, Aušra
Överby, Anna K.
Anastasina, Maria
Butcher, Sarah J.
author_facet Pulkkinen, Lauri I. A.
Barrass, Sarah V.
Domanska, Aušra
Överby, Anna K.
Anastasina, Maria
Butcher, Sarah J.
author_sort Pulkkinen, Lauri I. A.
collection PubMed
description Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.
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spelling pubmed-90274352022-04-23 Molecular Organisation of Tick-Borne Encephalitis Virus Pulkkinen, Lauri I. A. Barrass, Sarah V. Domanska, Aušra Överby, Anna K. Anastasina, Maria Butcher, Sarah J. Viruses Article Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions. MDPI 2022-04-11 /pmc/articles/PMC9027435/ /pubmed/35458522 http://dx.doi.org/10.3390/v14040792 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pulkkinen, Lauri I. A.
Barrass, Sarah V.
Domanska, Aušra
Överby, Anna K.
Anastasina, Maria
Butcher, Sarah J.
Molecular Organisation of Tick-Borne Encephalitis Virus
title Molecular Organisation of Tick-Borne Encephalitis Virus
title_full Molecular Organisation of Tick-Borne Encephalitis Virus
title_fullStr Molecular Organisation of Tick-Borne Encephalitis Virus
title_full_unstemmed Molecular Organisation of Tick-Borne Encephalitis Virus
title_short Molecular Organisation of Tick-Borne Encephalitis Virus
title_sort molecular organisation of tick-borne encephalitis virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027435/
https://www.ncbi.nlm.nih.gov/pubmed/35458522
http://dx.doi.org/10.3390/v14040792
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