Tick-borne encephalitis virus (TBEV) is an enveloped virus belonging to the family Flaviviridae, which causes severe disease of central nervous system in humans. The smooth virion surface is covered by envelope proteins (E-protein), that are together with the membrane proteins (M-protein) anchored in the virus lipid bilayer. The immature, non-infectious virus goes through a maturation phase during the viral life cycle. Proteolytic cleavage of prM and a significant rearrangement of the envelope proteins on the viral surface are two aspects of this process.
We isolated immature TBEV particles from infected tissue culture cells and visualized them using cryo-electron microscopy in order to determine their structure. The E-protein-prM-protein complex forms the "spiky" surface of the immature particles. Weused cryo-electron tomography and single-particle analysis to show that the TBEV immature particles are asymmetric. Defects induced during immature particle assembly frequently disturb the symmetric, icosahedral structure of the E-protein-prM-protein spikes on the particle surface. However, these irregularities do not hinder the subsequent maturation process and produce mature particles with vacant patches in the "herring bone" structure of the mature viral surface
The findings shed additional light on the viral assembly and maturation process, which may be the subject of future antiviral medication development.
This work was supported by the project National Institute of Virology and Bacteriology (Programme EXCELES, ID Project No. LX22NPO5103) - Funded by the European Union - Next Generation EU.