Nature communications, 2023-04, Vol.14 (1), p.2007-18, Article 2007
2023
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- Autor(en) / Beteiligte
- Titel
- Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
- Ist Teil von
- Nature communications, 2023-04, Vol.14 (1), p.2007-18, Article 2007
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2023
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combine multimodal imaging (cm-nm scale) with single nuclei RNA-sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar ) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection is imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection is limited to grey matter of sensory systems in wildtype mice, but extends into white matter, meninges and choroid plexus in Ifnar mice. Cells in wildtype display strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+ NK cells, whereas in Ifnar , the absence of this response contributes to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-023-37698-0Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1fe44396a5624497afce10ba6f02d443
- Format
- –
- Schlagworte
- Animals, Astrocytes, Brain, Brain - diagnostic imaging, Brain - metabolism, CD8 antigen, Choroid plexus, Encephalitis Viruses, Tick-Borne - genetics, Encephalitis Viruses, Tick-Borne - metabolism, Gene sequencing, Immune response, Infections, Interferon, Interferon Type I - metabolism, Macrophages, Medical imaging, Meninges, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, Molecular modelling, Neuroimaging, Neurons - metabolism, Pathogenesis, Receptor, Interferon alpha-beta - genetics, Receptor, Interferon alpha-beta - metabolism, Sensory systems, Substantia alba, Substantia grisea, Ticks - metabolism, Transcriptomics, Tropism, Vertebrates, Viral infections