ArticleThe Journal of clinical investigation2015
Human prion protein sequence elements impede cross-species chronic wasting disease transmission.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 84 citations in OpenAlex.
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- Prion propagation is controlled by discrete structural regions of PrP rather than overall stability.The Journal of biological chemistry · 2026Article
- Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease.Science advances · 2026Article
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Review
- Strain-Dependent Susceptibility to Prion Infection Encoded by Arg171 and Lys176 Sheep Prion Protein Polymorphic Variants.The Journal of infectious diseases · 2025Article
- Prion diseases: Lessons from historical outbreaks and potential emerging ones.Protein science : a publication of the Protein Society · 2025Review
- Variation in the prion protein gene (PRNP) open reading frame sequence in French cervids.Veterinary research · 2024Article
- Norwegian moose CWD induces clinical disease and neuroinvasion in gene-targeted mice expressing cervid S138N prion protein.PLoS pathogens · 2024Article
- Chronic Wasting Disease: State of the Science.Pathogens (Basel, Switzerland) · 2024Review
- A structural basis for prion strain diversity.Nature chemical biology · 2023Article
- Non-human primates in prion diseases.Cell and tissue research · 2023Review
- Vaccines for prion diseases: a realistic goal?Cell and tissue research · 2023Review
- Prion strains: shining new light on old concepts.Cell and tissue research · 2023Review
- Intrinsic determinants of prion protein neurotoxicity inFrontiers in molecular neuroscience · 2023Review
- Oral vaccination as a potential strategy to manage chronic wasting disease in wild cervid populations.Frontiers in immunology · 2023Review
- Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein.Veterinary research · 2022Article
- Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD.Acta neuropathologica · 2022Article
- Structural consequences of sequence variation in mammalian prion β2α2 loop segments.Frontiers in neuroscience · 2022Article
- MetNeuropathology and applied neurobiology · 2021Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.