Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
Issued Date
2023-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85152115180
Pubmed ID
37037810
Journal Title
Nature Communications
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.14 No.1 (2023)
Suggested Citation
Chotiwan N., Rosendal E., Willekens S.M.A., Schexnaydre E., Nilsson E., Lindqvist R., Hahn M., Mihai I.S., Morini F., Zhang J., Ebel G.D., Carlson L.A., Henriksson J., Ahlgren U., Marcellino D., Överby A.K. Type I interferon shapes brain distribution and tropism of tick-borne flavivirus. Nature Communications Vol.14 No.1 (2023). doi:10.1038/s41467-023-37698-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81318
Title
Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
Other Contributor(s)
Abstract
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.