Tick-borne encephalitis virus (TBEV) is an enveloped virus belonging to the family Flaviviridae. It is mainly transmitted by ticks and causes severe disease of central nervous system in humans. Virion surface is covered by envelope proteins (E-protein), that are together with the membrane proteins (M-protein) anchored in virus lipid bilayer. During the viral life cycle, the immature non-infectious virus undergoes a maturation process. This process includes proteolytic cleavage of prM and major reorganization of the envelope proteins on the viral surface.
To determine the structure of immature TBEV particles, we purified them from infected tissue culture cells and used cryo-electron microscopy for visualization. In comparison with smooth mature TBEV particles, the immature particles have “spiky” surface formed by the E-protein-prM-protein complex. We combined cryo-electron tomography and sub-tomogram averaging with single-particle analysis methods using localized reconstruction of the surface “spikes”, to determine the high-resolution structure of the immature E-protein complexes and their interaction with the prM-protein. The organization of the particle surface indicates that the TBEV maturation mechanism involves a complex reorganization of the envelope proteins on the viral surface.
The results show more detailed insight in the viral maturation process which may be targeted by specific antiviral drugs.