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Chapter 4: Pathogenesis of TBE

significantly increased dose-dependent TBEV the appearance of activated caspase 3
production, whereas the inhibition of following infection, and apoptosis in neurons
autophagy showed a dose-dependent occurs in the same areas where viral antigen is
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decrease of infectious virus. present. 15,16 In vitro, TBEV infection causes
apoptosis in mouse and human neural
Apoptosis cells. 17,18 Although brain-infiltrating CD8+ T
cells contribute to the fatal outcome during
Apoptosis is a process of programmed cell 19
infection no significant increase of apoptotic
death in which cells activate intracellular cell death was detectable upon infection with
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death pathways. This mechanism occurs in a Langat virus (LGTV) and TBEV in mice. 5,20
wide range of human viral infections, including These data are in line with human data, where
infections of the CNS such as herpes simplex
no prominent signs of neuronal apoptosis
virus (HSV) and cytomegalovirus (CMV) were seen in post-mortem brain tissue from
encephalitis. 13,14 In WNV infection of mice, patients.
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high virus titers in the CNS are associated with

Figure 2: Viral evasion of IFN induction

TBEV induces vesicles in the Endoplasmatic Reticulum (ER) where the viral RNA synthesis occurs. Early
during infection, these vesicles protect the dsRNA from cellular detection by RIG-I and/or MDA5. Later in
infection, high amounts of virus particles are produced and the dsRNA leaks out of the vesicles. The pattern
recognition receptors (PRRs) RIG-I and/or MDA5 then trigger signalling through IPS-1, phosphorylated IRF3
dimers are transported into the nucleus and IFN-β is upregulated. 28,38

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