Molecular Organisation of Tick-Borne Encephalitis Virus

Viruses. 2022 Apr 11;14(4):792. doi: 10.3390/v14040792.


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.

Keywords: TBEV; cryo-electron microscopy; envelope protein; glycoprotein; lipid factor; membrane protein; quasi-equivalence; tick-borne encephalitis virus.

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • Culicidae
  • Encephalitis Viruses, Tick-Borne* / genetics
  • Encephalitis Viruses, Tick-Borne* / ultrastructure
  • Encephalitis, Tick-Borne*
  • Viral Proteins / metabolism
  • Virion / metabolism
  • Virion / ultrastructure
  • Zika Virus / metabolism
  • Zika Virus Infection


  • Viral Proteins