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Chapter 2a: Virology

TBEV infection is associated with dramatic processes involved in morphogenesis, genome
morphological changes occurring in the replication, maturation, and genetic basis for
infected cells (Figure 7). These include virulence of flaviviruses, including TBEV.
formation of smooth membrane structures,
proliferation of endoplasmic reticulum, This has been made possible by the recent
reorganization of the Golgi complex, and advances in structural and biochemical
accumulation and convolution of membranes. techniques, and methods of molecular
Several cellular organelles are often biology, mainly site-directed mutagenesis.
damaged. 104–107 The infection is commonly However, several key questions related to
cytocidal; the infected cells often die by TBEV molecular biology and individual steps
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apoptosis or necrosis, but some vertebrate in the TBEV life-cycle remain unresolved.
cell types survive the lytic crisis and become Major gaps in our understanding of the TBEV
chronically infected. 108 replication strategy both in mammalian and
tick cells still exist. For instance, the nature of
It was found that NS3 protein from Langat the cellular receptor for virus entry into the
virus is able to activate cellular caspase-8 and host cell, mechanisms of viral genome release
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induce apoptosis of the host cell. On the from nucleocapsid, packaging of viral RNA by
other hand, tick cells do not undergo major the C protein, and virus maturation remain to
inhibition of host macromolecular synthesis be identified. Except for the E glycoprotein,
caused by the infection. No dramatic no structural data for the other TBEV proteins
cytopathic and ultrastructural changes are are available, and indeed the complete
seen in the infected tick cells and persistent functional role of some proteins remains
productive infection is established in these obscure. The role of specific RNA secondary
cells. 107,110–113 However, both vertebrate and structures present in TBEV untranslated
tick cells activate innate defense mechanisms genomic regions in viral RNA replication,
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against the infection. capping, and controlling the functions of non-
The TBEV maturation process in tick cells structural proteins, such as NS3 or NS5, need
seems, however, to be different from that to be established. These and other
observed in vertebrate cells. In a cell line unresolved problems highlight the necessity
derived from the tick Rhipicephalus for further research into the molecular,
appendiculatus infected with TBEV, nucleo- genetic, and structural properties of TBEV.
capsids are found in the cytoplasm and the Advances in our basic knowledge of TBEV
envelope is acquired by budding on biology should promote the development of
cytoplasmic membranes or into cellular more effective methods of controlling this
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vacuoles. important human pathogen.

Acknowledgments: DR was supported by the
Concluding remarks Ministry of Health of the Czech Republic,
grant No. 16-34238A. DR and KY were
The chapter summarized the major biological
supported by the project Mobility Plus JSPS-
features of TBEV, focusing particularly on virus 18-08 funded by the Czech Academy of
taxonomy, structure, genetics, and replication Sciences and Japanese Society for Promotion
strategy in host cells. The past 2 decades have of Science. MEB was supported by the
witnessed a tremendous progress in our
Intramural Research Program of the National
understanding of the structural, biochemical,
Institute of Allergy and Infectious Diseases of
and molecular aspects of a variety of the
the National Institutes of Health, USA. We

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