Type I interferon shapes brain distribution and tropism of tick-borne flavivirus

Nunya Chotiwan (), Ebba Rosendal, Stefanie M. A. Willekens, Erin Schexnaydre, Emma Nilsson, Richard Lindqvist, Max Hahn, Ionut Sebastian Mihai, Federico Morini, Jianguo Zhang, Gregory D. Ebel, Lars-Anders Carlson, Johan Henriksson, Ulf Ahlgren, Daniel Marcellino and Anna K. Överby ()
Additional contact information
Nunya Chotiwan: Umeå University
Ebba Rosendal: Umeå University
Stefanie M. A. Willekens: Umeå University
Erin Schexnaydre: Umeå University
Emma Nilsson: Umeå University
Richard Lindqvist: Umeå University
Max Hahn: Umeå University
Ionut Sebastian Mihai: Umeå University
Federico Morini: Umeå University
Jianguo Zhang: Umeå University
Gregory D. Ebel: Colorado State University
Lars-Anders Carlson: Umeå University
Johan Henriksson: Umeå University
Ulf Ahlgren: Umeå University
Daniel Marcellino: Umeå University
Anna K. Överby: Umeå University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37698-0

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