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Greenwood, A.D.* ; Vincendeau, M. ; Schmädicke, A.C.* ; Montag, J.* ; Seifarth, W.* ; Motzkus, D.*

Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis).

Mol. Neurodegener. 6:44 (2011)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. RESULTS: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. CONCLUSIONS: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cellular prion protein; Murine leukemia-virus; Opitz-syndrome gene; Mouse neuroblastoma-cells; Functional characterization; Nucleocapsid protein; Molecular-biology; Neuonal cells; RNA Expression; Envelope gene
e-ISSN 1750-1326
Quellenangaben Band: 6, Heft: 1, Seiten: , Artikelnummer: 44 Supplement: ,
Verlag BioMed Central
Begutachtungsstatus Peer reviewed