H2020 Marie Curie Actions of the European Commission
799929
European Union
H2020 Marie Curie Actions of the European Commission
765042
European Union
Swedish Research Council
2018-05851
スウェーデン
Academy of Finland
315950
フィンランド
Sigrid Juselius Foundation
95-7202-38
フィンランド
Jane and Aatos Erkko Foundation
フィンランド
引用
ジャーナル: Viruses / 年: 2022 タイトル: Molecular Organisation of Tick-Borne Encephalitis Virus. 著者: Lauri I A Pulkkinen / Sarah V Barrass / Aušra Domanska / Anna K Överby / Maria Anastasina / Sarah J Butcher / 要旨: Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family . Structural studies of flavivirus virions have primarily focused on mosquito-borne species, ...Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family . 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.