Analysis Tools
immune system
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• mice infected with tick-borne encephalitis virus (TBEV) show lower circulatory levels of IFN-beta at 4-days post-infection (dpi)
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• mice infected with TBEV show lower circulatory levels of IFN-gamma at 4 dpi
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• mice show a moderate increase in IL-6 level at baseline
• TBEV-infected mice show further elevation of IL-6 levels by 9 dpi
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• neurons of TBEV-infected mice often are accompanied by mild focal perivascular mononuclear infiltrates in the adjacent parenchyma that is consistent with mild nonsuppurative encephalitis, accompanied by mild microgliosis
• the infiltrating leukocytes in TBEV-infected mouse brain are mainly macrophages, with fewer T cells and rare B cells
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• TBEV-infected mice show an increase in liver inflammation, showing multifocal inflammatory cell infiltrations at the hepatic portal triad areas, the arterial walls, and in sinusoids with an increased number and size of inflammatory infiltrates at 4 dpi
• at 9 dpi with TBEV, mice show marked liver damage, displaying severe steatosis, multifocal mononuclear infiltrates (dominated by CD4+ helper T/CD8+ cytotoxic T lymphocytes and CD68+ macrophages
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• mice exhibit a greater sensitivity to tick-borne encephalitis virus (TBEV) infection due to a weak ability to elicit early mechanisms for viral defense (reduced induction of IFN-1-type innate immune response), while promoting inflammatory and neurodegenerative pathways
• TBEV-infected mice show lower circulatory levels of IFN-gamma and IFN-beta at 4-days dpi and 30-50% decreased expression of IFN-1 (IFNA4 and IFNB1), IFN receptor (IFNAR1), the PRR RIGI and ISGs (IF144, IF127, IFIT3, STAT1) in the cerebral cortex and/or spleen and moderately increased pro-inflammatory NF-kappaB-p65 and TNF
• TBEV-infected mice show low viral RNA in the liver at 9 dpi, but viral RNA in the brain is widespread and viral antigen is seen in neurons in olfactory bulb, cortex, brain stem, hippocampus, and medulla oblongada
• TBEV-infected mice show increased liver and brain inflammation, GABAergic neuron loss, and reduced nucleotide pools and mtDNA levels
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behavior/neurological
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• mice show a 20% decrease in treadmill and 30% decrease in rotarod performance at 12 months of age
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• mice show a slightly abnormal gait at 12 months of age
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cellular
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• the mtDNA copy number is decreased by around 30% in the liver and largely unchanged in the brain
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• mtDNA levels in the cerebral cortex on day 4 after TBEV infection are reduced to almost 50% of controls but no difference in the spleen or liver mtDNA amount is seen after TBEV infection
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• TBEV-infected mice show increased level of the necroptosis marker p-MLKL in the liver
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• mtDNA replication activity is decreased in the brain and liver
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homeostasis/metabolism
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• mice infected with tick-borne encephalitis virus (TBEV) show lower circulatory levels of IFN-beta at 4-days post-infection (dpi)
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• mice infected with TBEV show lower circulatory levels of IFN-gamma at 4 dpi
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• mice show a moderate increase in IL-6 level at baseline
• TBEV-infected mice show further elevation of IL-6 levels by 9 dpi
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• metabolome analysis of the cerebral cortex on day 4 after TBEV infection shows deceased nucleotide metabolism, especially the steady-state pools of pyrimidines required for cellular RNA and DNA synthesis
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liver/biliary system
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• the mtDNA copy number is decreased by around 30% in the liver and largely unchanged in the brain
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• TBEV-infected mice show an increase in liver inflammation, showing multifocal inflammatory cell infiltrations at the hepatic portal triad areas, the arterial walls, and in sinusoids with an increased number and size of inflammatory infiltrates at 4 dpi
• at 9 dpi with TBEV, mice show marked liver damage, displaying severe steatosis, multifocal mononuclear infiltrates (dominated by CD4+ helper T/CD8+ cytotoxic T lymphocytes and CD68+ macrophages
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• livers from TBEV-infected mice show occasional necrotic hepatocytes
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nervous system
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• mtDNA levels in the cerebral cortex on day 4 after TBEV infection are reduced to almost 50% of controls but no difference in the spleen or liver mtDNA amount is seen after TBEV infection
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• neurons of TBEV-infected mice often are accompanied by mild focal perivascular mononuclear infiltrates in the adjacent parenchyma that is consistent with mild nonsuppurative encephalitis, accompanied by mild microgliosis
• the infiltrating leukocytes in TBEV-infected mouse brain are mainly macrophages, with fewer T cells and rare B cells
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• mice show a reduction of GABAergic interneurons at 5 dpi with TBEV
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