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dc.contributor.authorCiurkiewicz, Malgorzata
dc.contributor.authorFloess, Stefan
dc.contributor.authorBeckstette, Michael
dc.contributor.authorKummerfeld, Maren
dc.contributor.authorBaumgärtner, Wolfgang
dc.contributor.authorHuehn, Jochen
dc.contributor.authorBeineke, Andreas
dc.identifier.citationBrain Pathol. 2021 Jul 6:e13000. doi: 10.1111/bpa.13000. Epub ahead of print.en_US
dc.description.abstractViral infections of the central nervous system cause acute or delayed neuropathology and clinical consequences ranging from asymptomatic courses to chronic, debilitating diseases. The outcome of viral encephalitis is partially determined by genetically programed immune response patterns of the host. Experimental infection of mice with Theiler's murine encephalomyelitis virus (TMEV) causes diverse neurologic diseases, including TMEV-induced demyelinating disease (TMEV-IDD), depending on the used mouse strain. The aim of the present study was to compare initial transcriptomic changes occurring in the brain of TMEV-infected SJL (TMEV-IDD susceptible) and C57BL/6 (TMEV-IDD resistant) mice. Animals were infected with TMEV and sacrificed 4, 7, or 14 days post infection. RNA was isolated from brain tissue and analyzed by whole-transcriptome sequencing. Selected differences were confirmed on a protein level by immunohistochemistry. In mock-infected SJL and C57BL/6 mice, >200 differentially expressed genes (DEGs) were detected. Following TMEV-infection, the number of DEGs increased to >700. Infected C57BL/6 mice showed a higher expression of transcripts related to antigen presentation via major histocompatibility complex (MHC) I, innate antiviral immune responses and cytotoxicity, compared with infected SJL animals. Expression of many of those genes was weaker or delayed in SJL mice, associated with a failure of viral clearance in this mouse strain. SJL mice showed prolonged elevation of MHC II and chemotactic genes compared with C57BL/6 mice, which presumably facilitates the induction of chronic demyelinating disease. In addition, elevated expression of several genes associated with immunomodulatory or -suppressive functions was observed in SJL mice. The exploratory study confirms previous observations in the model and provides an extensive list of new immunologic parameters potentially contributing to different outcomes of viral encephalitis in two mouse strains.en_US
dc.publisherWiley & Sons Ltd.en_US
dc.rightsAttribution 4.0 International*
dc.subjectTheiler's murine encephalomyelitis virusen_US
dc.subjectantigen presentationen_US
dc.subjectantiviral responseen_US
dc.subjectinnate immune responseen_US
dc.subjectmouse modelen_US
dc.subjectneurotropic virusen_US
dc.subjecttranscriptome analysisen_US
dc.subjectviral encephalitisen_US
dc.titleTranscriptome analysis following neurotropic virus infection reveals faulty innate immunity and delayed antigen presentation in mice susceptible to virus-induced demyelination.en_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalBrain pathology (Zurich, Switzerland)en_US
dc.source.journaltitleBrain pathology (Zurich, Switzerland)

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Attribution 4.0 International
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