Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>)
<p>Abstract</p> <p>Background</p> <p>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 provide...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-06-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/6/1/44 |
| _version_ | 1831559917833551872 |
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| author | Montag Judith Schmädicke Ann-Christin Vincendeau Michelle Greenwood Alex D Seifarth Wolfgang Motzkus Dirk |
| author_facet | Montag Judith Schmädicke Ann-Christin Vincendeau Michelle Greenwood Alex D Seifarth Wolfgang Motzkus Dirk |
| author_sort | Montag Judith |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Cynomolgus macaques (<it>Macaca fasicularis</it>) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the <it>basis pontis </it>and <it>vermis cerebelli </it>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-17T05:37:13Z |
| format | Article |
| id | doaj.art-509f0fb111104e0c9b5ac0133510fbc1 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-17T05:37:13Z |
| publishDate | 2011-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-509f0fb111104e0c9b5ac0133510fbc12022-12-21T22:01:35ZengBMCMolecular Neurodegeneration1750-13262011-06-01614410.1186/1750-1326-6-44Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>)Montag JudithSchmädicke Ann-ChristinVincendeau MichelleGreenwood Alex DSeifarth WolfgangMotzkus Dirk<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Cynomolgus macaques (<it>Macaca fasicularis</it>) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the <it>basis pontis </it>and <it>vermis cerebelli </it>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.</p> <p>Conclusions</p> <p>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.</p>http://www.molecularneurodegeneration.com/content/6/1/44 |
| spellingShingle | Montag Judith Schmädicke Ann-Christin Vincendeau Michelle Greenwood Alex D Seifarth Wolfgang Motzkus Dirk Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) Molecular Neurodegeneration |
| title | Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) |
| title_full | Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) |
| title_fullStr | Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) |
| title_full_unstemmed | Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) |
| title_short | Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (<it>Macaca fascicularis</it>) |
| title_sort | bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques it macaca fascicularis it |
| url | http://www.molecularneurodegeneration.com/content/6/1/44 |
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