CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection

Journal of Cellular Biochemistry
Sotirios Botsios, Laura Manuelidis

Abstract

Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure ...Continue Reading

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Citations

Jun 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yang-Hui YehLaura Manuelidis
Oct 15, 2018·Journal of Cellular Biochemistry·Laura Manuelidis
Jun 25, 2019·Journal of Cellular Biochemistry·Klara Szigeti-Buck, Laura Manuelidis
Mar 16, 2017·Current Obesity Reports·Jameson D Voss, Nikhil V Dhurandhar
Sep 22, 2018·Nature Reviews. Molecular Cell Biology·Matthew G IadanzaSheena E Radford
Jun 12, 2016·The Journal of Biological Chemistry·Jerson L Silva, Yraima Cordeiro
Aug 29, 2019·Scientific Reports·Petar Stefanov KovachevSuparna Sanyal
May 18, 2017·International Journal of Molecular Sciences·Bruno Macedo, Yraima Cordeiro
Nov 28, 2018·JAD Reports·Richard Lathe, Jean-Luc Darlix

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