Year: 2023
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: Kempe Foundation, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Umeå Universitet, Kempestiftelserna, Umeå Centre for Microbial Research, Stockholms Universitet, Science for Life Laboratory, National Institutes of Health, Center for Exercise Medicine, University of Alabama at Birmingham, Institutionen för Integrativ Medicinsk Biologi, Umeå Universitet, Wallenberg Centre for Molecular and Translational Medicine, National Institute of Allergy and Infectious Diseases
Awards: G1636562685, G1852685581, G1986533710, G2252777492, G3010212676, Novel imaging approaches to study islet dysfunction intype 1 and type 2 diabetes, G3471652666, G3584431731, G4501282839, National Microscopy Infrastructure, G4919463464, G5605728416, MIMS - The Swedish EMBL node for Molecular Infection Medicine, G6318280580, Viral tropism and host responses in the brain, G712881263, G7759244229, Multimodal imaging and proteomics to study flavivirus replication and molecular disease mechanisms, G8019152275
OpenAlex ID: W4363674796