Page 95 - TBE_Book_V2_2019

Chapter 4: Pathogenesis of TBE

Type I IFN response most studied. Type I IFNs binds to the IFNα
receptor (IFNAR), which is expressed on nearly
The type I IFN system is the first line of all cell types, and reacts in a paracrine and
defense against viral infection and an autocrine manner. The IFNAR is composed of
important part of the intrinsic innate immune a heterodimer of IFNAR1 and IFNAR2. After
response that controls virus dissemination and binding of IFN, the IFNAR activates the Janus
protects against serious disease. This response kinases, Jak1 and Tyk2, which then phosphor-
rapidly detects invading pathogens and rylate the signal transducer and activator of
upregulates inhibitory effector proteins and transcription (STAT)-1 and STAT2 proteins,
cytokines to ensure survival. The detection of resulting in activation and trans-location of
pathogens is based on recognition of the non- the IFN-stimulated gene 3 (ISGF3) transcript-
self-pathogen-associated molecular pattern tion factor complex into the nucleus. This
(PAMP) by specific host sensors, the pattern ISGF3 induces hundreds of IFN stimulated
recognition receptors (PRR). This leads to a genes (ISGs), that encode proteins with
signaling cascade and the upregulation and diverse biological function and some are
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secretion of IFN. IFNs are a large family of potent antiviral proteins and part of the
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cytokines where the IFNα and -β are type I response against mammalian viruses.
IFNs and IFNγ is type II IFNs and these are the

Figure 3: Viperin overexpression inhibits European TBEV growth by 4 orders of
magnitude

TBEV replication in cells expressing different interferon-stimulated genes (ISG). Cells tetracycline-induced to
express different ISGs were used to identify ISGs that inhibit TBEV replication. Cells expressing a reporter
gene (CAT) and CAT-expressing cells pretreated with IFNα were used as controls. Virus growth in ISG-induced
cells were compared to uninduced cells. Titers of TBEV were measured at 24 hours post-infection and 64
hours after tetracycline induction. The titers shown are mean log10 pfu/mL values from 3 independent
experiments; error bars are standard deviations.

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