Page 50 - TBE_Book_V2_2019

Chapter 2b: The molecular and antigenic structure of TBEV

Table 1. Furin cleavage sites of different flaviviruses

Virus Strain Amino acid (AA) AA sequence GenBank
sequence pr M Accession no.
c
b
P14 P1 a P1‘ P6‘
TBEV Neudoerfl YGRCGKQEGS--RTRR SVLIPSH U27495
POW virus LB YGRCGRQAGS--RGKR SVVIPTH L06436
DEN-1 SG/07K3640DK1/20 YGTC-SQTGEHRRDKR SVALAPH GQ398255
virus 08
Zika virus H/PF/2013 YGTCHHKKGEARRSRR AVTLPSH KJ776791
WNV NY_99 YGRC-TKTRHSRRSRR SLTVQTH DQ211652
YFV Asibi YGKC-DSAGRSRRSRR AIDLPTH AY640589
a
The arrow indicates the proteolytic cleavage site.
b
Sequence positions P1 to P14 (TBEV numbers) upstream of cleavage site (pr part),
dibasic motif in bold letters (P1, P2)
c
Sequence positions P’1 to P’6 downstream of cleavage site (M protein)
immature and mature virions are available for Virus particle structures and life
closely related mosquito-borne flaviviruses
(such as dengue, West Nile, Japanese cycle
encephalitis, and Zika viruses) 13-25 and form the
basis for understanding the viral life cycles and Virus assembly, maturation and
interactions with antibodies at a molecular release
level. Recently, a high-resolution cryo-EM
structure of mature TBEV was published by Virus assembly takes place in the endoplasmic
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Fuzik et al., providing for the first time details reticulum (ER) and leads to the formation of
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of the particle organization and interactions of immature particles (Figure 1C,E and Figure 2).
proteins in a flavivirus transmitted by ticks This first assembly product contains three
(Figure 1B,G). structural proteins: C (capsid), forming an ill-
defined spherical core together with the viral
Here, we review the structure of TBEV with a genomic RNA, and two membrane associated
focus on the role of E in the viral life cycle and proteins, prM (precursor of M) and E in a
as a major determinant for the induction of heterodimeric complex. Trimers of these het-
virus neutralizing antibodies. These properties erodimers form spikes at the surface of im-
are discussed in the context of what is known mature particles that are non-infectious (Figure
for other flaviviruses, in order to provide a more 1C,E).
rounded picture of TBEV structure-function
relationships and to emphasize the gaps that Studies with TBEV have provided evidence that
still exist in our understanding of the structural prM functions as a chaperone for the correct
foundations of TBEV biology. folding of E during its biosynthesis, at least in
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certain cellular environments. Experiments
with recombinantly expressed prM and E
proteins in mammalian cells (COS-1) revealed
that heterodimerization of the two proteins
occurs rapidly and is important for the final
folding steps. On the one hand, E apparently
requires prM to reach its native conformation
efficiently and on the other hand, prM needs E

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