Document Detail


Search for a prion-specific nucleic acid.
MedLine Citation:
PMID:  16051871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.
Authors:
Jiri G Safar; Klaus Kellings; Ana Serban; Darlene Groth; James E Cleaver; Stanley B Prusiner; Detlev Riesner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  79     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-29     Completed Date:  2005-09-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10796-806     Citation Subset:  IM    
Affiliation:
Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism
Centrifugation, Density Gradient
Cricetinae
Ethanol / pharmacology
Mesocricetus
Nucleic Acids / analysis*
Prions / genetics*,  metabolism,  radiation effects
RNA / analysis
Ultraviolet Rays
Zinc / pharmacology
Grant Support
ID/Acronym/Agency:
AG02132/AG/NIA NIH HHS; AG021601/AG/NIA NIH HHS; AG10770/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Nucleic Acids; 0/Prions; 63231-63-0/RNA; 64-17-5/Ethanol; 7440-66-6/Zinc
Comments/Corrections

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


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