Abstract
AbstractViral 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.
Funder
Knut och Alice Wallenbergs Stiftelse
Kempestiftelserna
Umeå University Industrial Doctoral School
Vetenskapsrådet
Wallenberg Centre for Molecular Medicine Umeå
The Laboratory for Molecular Infection Medicine Sweden
Umeå University Medical Faculty
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference84 articles.
1. Sips, G. J., Wilschut, J. & Smit, J. M. Neuroinvasive flavivirus infections. Rev. Med Virol. 22, 69–87 (2012).
2. Gosztonyi, G. & Koprowski, H. The concept of neurotropism and selective vulnerability (“pathoclisis”) in virus infections of the nervous system–a historical overview. Curr. Top. Microbiol Immunol. 253, 1–13 (2001).
3. Sejvar, J. J. The long-term outcomes of human West Nile virus infection. Clin. Infect. Dis. 44, 1617–1624 (2007).
4. Turtle, L., Griffiths, M. J. & Solomon, T. Encephalitis caused by flaviviruses. QJM 105, 219–223 (2012).
5. Gould, E. A. & Solomon, T. Pathogenic flaviviruses. Lancet 371, 500–509 (2008).
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