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Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination

Ulrich, Reiner ; Puff, Christina ; Wewetzer, Konstantin ; Kalkuhl, Arno ; Deschl, Ulrich ; Baumgärtner, Wolfgang Subbiah, Elankumaran

PloS one, 2014-04, Vol.9 (4), p.e95917-e95917 [Peer Reviewed Journal]

United States: Public Library of Science

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Title:
Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination
Author: Ulrich, Reiner ; Puff, Christina ; Wewetzer, Konstantin ; Kalkuhl, Arno ; Deschl, Ulrich ; Baumgärtner, Wolfgang
Subbiah, Elankumaran
Subjects: Age ; Analysis ; Animals ; Antigens ; Biology and Life Sciences ; Brain - pathology ; Brain - virology ; Canine distemper ; Canine distemper virus ; Care and treatment ; CD3 antigen ; Cerebellum ; Correlation analysis ; Cytotoxicity ; Demyelinating Diseases - genetics ; Demyelinating Diseases - metabolism ; Demyelinating Diseases - veterinary ; Demyelination ; Diagnosis ; Disease ; Diseases ; Distemper - genetics ; Distemper - metabolism ; Distemper - virology ; Distemper Virus, Canine - physiology ; Distribution ; DNA microarrays ; Dogs ; Down-Regulation ; Dystrophy ; Encephalitis ; Expressed sequence tags ; Female ; Gene expression ; Gene Ontology ; Gene regulation ; Gene set enrichment analysis ; Genes ; Genetic Markers ; Genomes ; Immune response ; Immune response (cell-mediated) ; Immune response (humoral) ; Immune system ; Immunohistochemistry ; Infections ; Inflammation ; Leukoencephalitis ; Leukoencephalopathies - genetics ; Leukoencephalopathies - metabolism ; Leukoencephalopathies - veterinary ; Lymphocytes T ; Male ; Medicine and Health Sciences ; Molecular Sequence Annotation ; Morphology ; Morphometry ; Multiple sclerosis ; Myelin ; Myelin basic protein ; Myelin proteins ; Nervous system ; Neuroglia - metabolism ; Neuroglia - virology ; Neurosciences ; Panencephalitis ; Pathogenesis ; Pathology ; Product safety ; Protein arrays ; Proteolipid protein ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Subacute sclerosing panencephalitis ; Transcription ; Transcriptome ; Up-Regulation ; Veterinary medicine ; Viruses
Is Part Of: PloS one, 2014-04, Vol.9 (4), p.e95917-e95917
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: Arno Kalkuhl and Ulrich Deschl are employed by Boehringer Ingelheim Pharma GmbH&Co KG. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: RU KW UD WB. Performed the experiments: RU CP AK. Analyzed the data: RU CP AK. Contributed reagents/materials/analysis tools: RU CP AK UD WB. Wrote the paper: RU WB.
Description: 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".
Publisher: United States: Public Library of Science
Language: English

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Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination

Ulrich, Reiner ; Puff, Christina ; Wewetzer, Konstantin ; Kalkuhl, Arno ; Deschl, Ulrich ; Baumgärtner, Wolfgang Subbiah, Elankumaran

United States: Public Library of Science

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