Document Detail

Strain-specific viral properties of variant Creutzfeldt-Jakob disease (vCJD) are encoded by the agent and not by host prion protein.
MedLine Citation:
PMID:  19097123     Owner:  NLM     Status:  MEDLINE    
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.
Laura Manuelidis; Ying Liu; Brian Mullins
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  106     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-27     Completed Date:  2009-03-04     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  220-31     Citation Subset:  IM    
Yale Medical School, 333 Cedar Street, New Haven, Connecticut 06510, USA.
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MeSH Terms
Biological Markers / metabolism
Creutzfeldt-Jakob Syndrome / etiology*,  metabolism,  transmission,  virology*
Prion Diseases / metabolism,  transmission,  virology
Prions / genetics*,  metabolism
Serial Passage
Species Specificity
Grant Support
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
Reg. No./Substance:
0/Biological Markers; 0/Prions

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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