| Strain-specific viral properties of variant Creutzfeldt-Jakob disease (vCJD) are encoded by the agent and not by host prion protein. | |
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MedLine Citation:
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PMID: 19097123 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human CJD, endemic sheep scrapie, epidemic bovine spongiform encephalopathy (BSE), and other transmissible spongiform encephalopathies (TSEs), are caused by a group of related but molecularly uncharacterized infectious agents. The UK-BSE agent infected many species, including humans where it causes variant CJD (vCJD). As in most viral infections, different TSE disease phenotypes are determined by both the agent strain and the host species. TSE strains are most reliably classified by incubation time and regional neuropathology in mice expressing wild-type (wt) prion protein (PrP). We compared vCJD to other human and animal derived TSE strains in both mice and neuronal cultures expressing wt murine PrP. Primary and serial passages of the human vCJD agent, as well as the highly selected mutant 263K sheep scrapie agent, revealed profound strain-specific characteristics were encoded by the agent, not by host PrP. Prion theory posits that PrP converts itself into the infectious agent, and thus short incubations require identical PrP sequences in the donor and recipient host. However, wt PrP mice injected with human vCJD brain homogenates showed dramatically shorter primary incubation times than mice expressing only human PrP, a finding not in accord with a PrP species barrier. All mouse passage brains showed the vCJD agent derived from a stable BSE strain. Additionally, both vCJD brain and monotypic neuronal cultures produced a diagnostic 19 kDa PrP fragment previously observed only in BSE and vCJD primate brains. Monotypic cultures can be used to identify the intrinsic, strain-determining molecules of TSE infectious particles. |
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Authors:
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Laura Manuelidis; Ying Liu; Brian Mullins |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 106 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-27 Completed Date: 2009-03-04 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 220-31 Citation Subset: IM |
Affiliation:
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Yale Medical School, 333 Cedar Street, New Haven, Connecticut 06510, USA. laura.manuelidis@yale.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Cattle Creutzfeldt-Jakob Syndrome / etiology*, metabolism, transmission, virology* Cricetinae Humans Prion Diseases / metabolism, transmission, virology Prions / genetics*, metabolism Serial Passage Sheep Species Specificity |
| Grant Support | |
ID/Acronym/Agency:
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1R21AI076645./AI/NIAID NIH HHS; NS012674/NS/NINDS NIH HHS; R01 NS012674-31/NS/NINDS NIH HHS; R21 AI076645-02/AI/NIAID NIH HHS; R56 NS012674-30A1/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Prions |
| Comments/Corrections | |
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