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Chapter 2a: Virology

viruses is relatively slower than that of the In the trans-Golgi compartment, the pr is
mosquito-transmitted viruses. In addition, the cleaved from prM by a cell furin-like protease;
evolution is not significantly influenced by this is followed by the conformational change,
migratory birds or international trade. 23 rotation, and rearrangement of E proteins
from 60 antiparallel trimers into 90 anti-

parallel dimers, forming an unusual ‘herring-
Virion structure and morphology bone’ pattern with icosahedral symmetry and
resulting in the viral particles being mature
Infectious TBEV virions are small spherical and fully infectious. However, the efficiency of
particles about 50 nm in diameter with no prM cleavage varies for different flaviviruses;
obvious distinct projections. The mature cleavage is therefore not always absolute.
virions contain an electron-dense core Thus, immature particles may also be released
approximately 30 nm in diameter which is as a proportion of the infectious/ non-
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surrounded by a lipid bilayer (Figure 2). The infectious virus pool.
nucleocapsid core consists of single-stranded
positive-polarity genomic ribonucleic acid The structure of purified TBEV particles has
(RNA) molecule (11 kb) and the capsid protein recently been determined at near atomic
C (12 kDa). The surface of the lipid membrane resolution of 3.9 Å by reconstruction of cryo-
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incorporates an envelope glycoprotein (E, 53K) electronmicroscopic images (Figure 2). The
and a membrane glycoprotein (M, 8K) (Figure study revealed a relatively smooth outer
2). surface of the particle, and E and M proteins
organized in a similar manner to that in other
The glycosylated E protein is also a major flaviviruses. The surface of the TBEV virion is
antigenic determinant of the virus and induces covered with small protrusions formed by gly-
immune responses in infected mammalian cans attached to the E-protein molecules. 119
hosts. It also contains the sites for virus Both E-proteins and M-proteins are anchored
binding to receptors on the surface of suscep- in the virion membrane, each by two trans-
tible host cells and subsequent pH-mediated membrane helices. Viral envelope membrane
fusion of the viral E protein with endosomal is not spherical; instead the shape of the
membranes during entry of viral RNA into the membrane closely follows the inner surface of
cell. the protein envelope and is deformed by
insertions of the trans-membrane helices of E-
In the mature infectious virions, the M protein proteins and M-proteins. 119
has been proteolytically cleaved from the
precursor (pr)M protein. This post- RSPs are of T-1 icosahedral symmetry formed
translational process occurs during the by 30 E protein dimers. RSPs have the same
maturation of nascent viral particles within antigenic properties as wild-type virus. They
the secretory pathway and immediately can be used for vaccination purposes and
before release of the infectious virions from represent an established model system for
the infected cell. In immature non-infectious flavivirus membrane fusion because they have
particles, prM and E proteins form hetero- fusion characteristics similar to those of
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dimers and exist as trimers covering the virion infectious virions.
surface. At this stage, the pr part of prM

occludes the fusion domain of the E Viral genome
glycoprotein, preventing premature fusion
with cell membranes within the secretory The nucleocapsid is formed from a single viral
pathway (Figure 3). RNA genome and multiple copies of the C
protein. The RNA binding domains of the C

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