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

Author

Listed:
  • Nunya Chotiwan

    (Umeå University
    Umeå University
    Mahidol University)

  • Ebba Rosendal

    (Umeå University
    Umeå University)

  • Stefanie M. A. Willekens

    (Umeå University
    Umeå University
    Umeå University)

  • Erin Schexnaydre

    (Umeå University
    Umeå University
    Umeå University
    Umeå University)

  • Emma Nilsson

    (Umeå University
    Umeå University)

  • Richard Lindqvist

    (Umeå University
    Umeå University)

  • Max Hahn

    (Umeå University)

  • Ionut Sebastian Mihai

    (Umeå University
    Umeå University
    Umeå University)

  • Federico Morini

    (Umeå University)

  • Jianguo Zhang

    (Umeå University
    Umeå University
    Umeå University
    Umeå University)

  • Gregory D. Ebel

    (Colorado State University)

  • Lars-Anders Carlson

    (Umeå University
    Umeå University
    Umeå University
    Umeå University)

  • Johan Henriksson

    (Umeå University
    Umeå University
    Umeå University)

  • Ulf Ahlgren

    (Umeå University)

  • Daniel Marcellino

    (Umeå University)

  • Anna K. Överby

    (Umeå University
    Umeå University)

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.

Suggested Citation

  • 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 &, 2023. "Type I interferon shapes brain distribution and tropism of tick-borne flavivirus," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37698-0
    DOI: 10.1038/s41467-023-37698-0
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    1. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
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