Page 33 - TBE_Book_V2_2019

Chapter 2a: Virology

Figure 6

Schematic illustration of the TBEV life cycle. (1) Infection begins with the binding of viral particles to specific
cell-surface receptors, which have not yet been unequivocally identified. (2) Viral particles enter cells via
endocytic pathway. (3) Low pH in the late endosome triggers conformational changes in the E proteins,
leading to rearrangement of dimers to trimeric forms (fusogenic state) and the subsequent fusion of the viral
envelope with endosomal membranes, which leads to virion uncoating. (4) Replication of the virus occurs
through the synthesis of anti-sense (negative) RNA, which serves as the template for genome RNA production.
Replication complexes are localized in membranous structures within the endoplasmic reticulum (ER). (5)
Assembled nucleocapsids acquire lipid envelopes by budding into the ER lumen. (6) Immature particles pass
through the Golgi complex. (7) Maturation takes place in the trans-Golgi network, involving the cleavage of
prM and the reorganization of E proteins into fusion-competent homodimers, leading to a change from spiky
immature to smooth mature particles. (8) Mature particles are transported in cytoplasmic vesicles and
released into the extracellular space by exocytosis.
Reproduced from Ruzek et al., Antiviral Res. 2019 Jan 30. pii: S0166-3542(18)30447-9. doi: 10.1016/
j.antiviral.2019.01.014. with permission from Elsevier.

development of the functionally important SfRNA results from incomplete degradation of
secondary RNA structures in the 3′-UTR. viral RNA by the cellular 5’-3’ exoribonuclease
Subsequent formation of extended RNA XRN1. The exoribonuclease activity stops at
domains evolved as promoters and enhancers the highly ordered RNA secondary structures
of virus replication determined by the at the beginning of the 3′-UTR. SfRNA is
selective requirements of the vertebrate and involved in modulating multiple cellular
invertebrate hosts. 38,48,49 pathways; e.g., inhibiting antiviral activity of
type I interferons (IFN) and RNAi pathways,
Flaviviruses, including TBFVs, are known to facilitating viral pathogenicity. 50
produce unique non-coding subgenomic RNA
(sfRNA), which is derived from the 3′-UTR.

28
28