Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?

In canine distemper demyelinating leukoencephalitis (DL), caused by canine distemper virus (CDV), astrocytes represent the main virus target. In these cells, glial fibrillary acidic protein (GFAP) is the main intermediate filament, whereas vimentin occurs early in the astrocytic lineage and is repla...

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Bibliographic Details
Published in:	Acta neuropathologica Vol. 114; no. 6; pp. 597 - 608
Main Authors:	Seehusen, Frauke, Orlando, Enzo A, Wewetzer, Konstantin, Baumgärtner, Wolfgang
Format:	Journal Article
Language:	English
Published:	Germany Springer Nature B.V 01-12-2007
Subjects:	Alzheimer's disease Animals Astrocytes - metabolism Astrocytes - pathology Astrocytes - virology Brain - virology Cell culture Cells, Cultured Chronic Disease Demyelinating Diseases - pathology Demyelinating Diseases - physiopathology Demyelinating Diseases - virology Disease Distemper - pathology Distemper - physiopathology Distemper - virology Distemper Virus, Canine - pathogenicity Distemper Virus, Canine - physiology Dogs Encephalomyelitis - pathology Encephalomyelitis - physiopathology Encephalomyelitis - virology Fluorescent Antibody Technique Giant Cells - metabolism Giant Cells - pathology Giant Cells - virology Glial Fibrillary Acidic Protein - metabolism Immunity, Innate - physiology Immunohistochemistry Infections Intermediate Filaments - metabolism Intermediate Filaments - ultrastructure Morphology Multiple sclerosis Neuropathology Pathology Proteins Tumor necrosis factor-TNF Veterinary medicine Vimentin - metabolism Germany
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Summary:	In canine distemper demyelinating leukoencephalitis (DL), caused by canine distemper virus (CDV), astrocytes represent the main virus target. In these cells, glial fibrillary acidic protein (GFAP) is the main intermediate filament, whereas vimentin occurs early in the astrocytic lineage and is replaced gradually by GFAP. To further characterize the role of astrocytic infection in dogs with DL, an animal model for multiple sclerosis, formalin-fixed paraffin-embedded cerebella were investigated immunohistochemically and by immunofluorescence. The expression and morphological alterations of these intermediate filaments were also determined by immunofluorescence studies of CDV-infected canine mixed brain cell cultures. In acute distemper lesions, the astrocytic response was mainly composed of GFAP- and CDV-positive cells. In contrast, vimentin-positive astrocyte-like cells were present in advanced lesions, which represented the main cell type harboring the pathogen, indicating a change in cell tropism and/or susceptibility of glial cells during lesion progression in CDV encephalomyelitis. Canine cell cultures were composed of GFAP-positive astrocytes, vimentin-positive cells and other glial cells. Following infection with the CDV-R252 strain, GFAP-positive astrocytes, especially multinucleated syncytial giant cells, displayed a disrupted cytoskeleton, whereas vimentin-positive cells though more frequently infected did not show any alteration in the filament network. This indicates increased vulnerability of mature GFAP-positive astrocytes compared to immature, vimentin-positive astrocytes. The latter, however, exhibited increased susceptibility to CDV. To conclude, the present findings indicate a change in cell tropism of CDV and/or the occurrence of less differentiated astrocytes representing a permanent source for virus infection and spread in advanced lesions of DL.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0001-6322 1432-0533
DOI:	10.1007/s00401-007-0307-5