Key result
Canine distemper virus-induced leukoencephalitis was associated with 780 differentially expressed probe sets, characterized by up-regulation of immune response genes and selective down-regulation of myelin genes in subacute cases.
Case-Control (n=26)
Yes
Transcriptional profiling of CDV-induced leukoencephalitis in dogs supports a biphasic mode of demyelination, involving early oligodendrocyte dystrophy and late immune-mediated demyelination.
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Hypothesis-generating for biphasic demyelination in viral encephalitis; extends animal transcriptional models but leaves open human translation.
Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".
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Ulrich et al. (2014) conducted a case-control in Canine Distemper Virus-Induced Demyelinating Leukoencephalitis (n=26). Canine Distemper Virus (CDV) infection vs. Non-infected control dogs was evaluated on Differentially expressed probe sets (transcriptional changes) in cerebellar specimens. Canine distemper virus-induced leukoencephalitis was associated with 780 differentially expressed probe sets, characterized by up-regulation of immune response genes and selective down-regulation of myelin genes in subacute cases.
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