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Chapter 2b: The molecular and antigenic structure of TBEV

Figure 2: Life-cycle of flaviviruses

Left: Virus entry. Viruses are taken up by receptor-mediated endocytosis and low pH in endosomes triggers viral
membrane fusion, resulting in the release of the viral genome into the cytoplasm. Protein translation and RNA
replication occur at virus-induced ER membranes.
Right: Virus assembly, maturation and release. Formation of immature virions takes place by a budding process
into the ER. As a byproduct, subviral particles are formed that are devoid of a nucleocapsid. Particles are
transported through the exocytic pathway. The acidic pH in the TGN causes a major structural rearrangement
that leads to the formation of an E herringbone-like arrangement that is characteristic of mature virions (see
Figure 1) and exposes the furin cleavage site in prM. The cleaved-off pr segment of prM remains associated with
E at acidic pH but falls off at the neutral pH of the extracellular fluid upon secretion of the particles.
Color code of prM and E as in Figure 1.

including dengue viruses, West Nile virus In terms of their structure, flaviviruses are today
(WNV), Japanese encephalitis virus (JEV), Zika among the best studied enveloped viruses.
virus and Yellow fever virus (YFV), 2-11 which Importantly, new technologies and instrumen-
gives the name to the genus Flavivirus in the tation have led to the elucidation of structural
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family Flaviviridae. All of these structures have details not only of the isolated E protein but
the same overall protein architecture as the also of whole virus particles using electron
TBEV E protein. cryomicroscopy (cryo EM). Structures of both

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