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In Situ Photodegradation of Incorporated Polyanion Does Not Alter Prion Infectivity

Authors
Journal
PLoS Pathogens
1553-7366
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
2
Identifiers
DOI: 10.1371/journal.ppat.1002001
Keywords
  • Research Article
  • Medicine
  • Infectious Diseases
  • Prion Diseases
  • Veterinary Science
  • Veterinary Diseases
  • Zoonotic Diseases
Disciplines
  • Biology
  • Medicine
  • Physics

Abstract

Single-stranded polyanions ≥40 bases in length facilitate the formation of hamster scrapie prions in vitro, and polyanions co-localize with PrPSc aggregates in vivo [1], [2]. To test the hypothesis that intact polyanionic molecules might serve as a structural backbone essential for maintaining the infectious conformation(s) of PrPSc, we produced synthetic prions using a photocleavable, 100-base oligonucleotide (PC-oligo). In serial Protein Misfolding Cyclic Amplification (sPMCA) reactions using purified PrPC substrate, PC-oligo was incorporated into physical complexes with PrPSc molecules that were resistant to benzonase digestion. Exposure of these nuclease-resistant prion complexes to long wave ultraviolet light (315 nm) induced degradation of PC-oligo into 5 base fragments. Light-induced photolysis of incorporated PC-oligo did not alter the infectivity of in vitro-generated prions, as determined by bioassay in hamsters and brain homogenate sPMCA assays. Neuropathological analysis also revealed no significant differences in the neurotropism of prions containing intact versus degraded PC-oligo. These results show that polyanions >5 bases in length are not required for maintaining the infectious properties of in vitro-generated scrapie prions, and indicate that such properties are maintained either by short polyanion remnants, other co-purified cofactors, or by PrPSc molecules alone.

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