Generation of a New Form of Human PrPSc in Vitro by Interspecies Transmission from Cervid Prions*

Prion diseases are infectious neurodegenerative disorders that affect humans and animals and that result from the conversion of normal prion protein (PrPC) into the misfolded prion protein (PrPSc). Chronic wasting disease (CWD) is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. Determining the risk of transmission of CWD to humans is of utmost importance, considering that people can be infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the misfolded form by CWD PrPSc, we performed experiments using the protein misfolding cyclic amplification technique, which mimics in vitro the process of prion replication. Our results show that cervid PrPSc can induce the conversion of human PrPC but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, the newly generated human PrPSc exhibits a distinct biochemical pattern that differs from that of any of the currently known forms of human PrPSc. Our results also have profound implications for understanding the mechanisms of the prion species barrier and indicate that the transmission barrier is a dynamic process that depends on the strain and moreover the degree of adaptation of the strain. If our findings are corroborated by infectivity assays, they will imply that CWD prions have the potential to infect humans and that this ability progressively increases with CWD spreading.

• Publication year

  2011

• Venue

  Journal of Biological Chemistry

• Publication date

  2011-01-05

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1074/jbc.M110.198465PMID 21209079PMCID PMC3045004
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• De Novo Generation of Infectious Prions In Vitro Produces a New Disease Phenotype

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• Trans-species amplification of PrP(CWD) and correlation with rigid loop 170N.

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• Susceptibilities of Nonhuman Primates to Chronic Wasting Disease

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  2008cited by this paper
• In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification.

  2008cited by this paper
• Cell‐free propagation of prion strains

  2008cited by this paper
• Chronic wasting disease.

  2007cited by this paper
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• Formation of native prions from minimal components in vitro

  2007cited by this paper
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• Ultra-efficient Replication of Infectious Prions by Automated Protein Misfolding Cyclic Amplification*

  2006cited by this paper
• Transmission of Elk and Deer Prions to Transgenic Mice

  2006cited by this paper
• How to find a prion: [URE3], [PSI+] and [beta].

  2006cited by this paper
• Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

  2006cited by this paper
• Protein misfolding cyclic amplification for diagnosis and prion propagation studies.

  2006cited by this paper
• Detection of prions in blood

  2005cited by this paper
• Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models

  2005cited by this paper
• Cyclic amplification of protein misfolding and aggregation.

  2005cited by this paper
• Pre‐symptomatic detection of prions by cyclic amplification of protein misfolding

  2005cited by this paper
• Species barriers in prion diseases--brief review.

  2005cited by this paper
• Interspecies Transmission of Chronic Wasting Disease Prions to Squirrel Monkeys (Saimiri sciureus)

  2005cited by this paper
• In vitro generation of infectious scrapie prions.

  2005cited by this paper
• Transmission of Prions from Mule Deer and Elk with Chronic Wasting Disease to Transgenic Mice Expressing Cervid PrP

  2004cited by this paper
• Chronic wasting disease of cervids.

  2004cited by this paper
• Toxicogenomics: roadblocks and new directions.

  2003cited by this paper
• Subclinical scrapie infection in a resistant species: persistence, replication, and adaptation of infectivity during four passages.

  2002cited by this paper
• Bovine spongiform encephalopathy, chronic wasting disease, scrapie, and the threat to humans from prion disease epizootics

  2002cited by this paper
• Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding

  2001cited by this paper
• Creutzfeldt-Jakob disease in unusually young patients who consumed venison.

  2001cited by this paper
• Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD

  1996cited by this paper
• Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein.

  1995cited by this paper
• Survival of scrapie virus after 3 years' interment.

  1991cited by this paper
• Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins

  1987cited by this paper

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• Genetic Variation and Strain Dynamics in Chronic Wasting Disease

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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
• Chronic Wasting Disease Prion Strain Emergence and Host Range Expansion

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
• Human prion protein sequence elements impede cross-species chronic wasting disease transmission.

  2015cites this paper
• Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus)

  2015cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
• Genetic assessment of environmental features that influence deer dispersal: implications for prion-infected populations

  2014cites this paper
• Molecular Barriers to Zoonotic Transmission of Prions

  2014cites this paper
• Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005-2011.

  2014cites this paper
• Bovine Spongiform Encephalopathy Induces Misfolding of Alleged Prion-Resistant Species Cellular Prion Protein without Altering Its Pathobiological Features

  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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