ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural effects of PrP polymorphisms on intra- and interspecies prion transmission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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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Who cites it
45 citing papers in PubMed, 49 citations in OpenAlex.
- Distinct prion conformers from brain and peripheral tissues of gene-targeted mice produce convergent CWD strain properties.PLoS pathogens · 2026Article
- Odocoileus virginianus PRNP sequencing reveals AF (QVeterinary research · 2026Article
- Novel Prion Protein Gene (bioRxiv : the preprint server for biology · 2026Article
- Identification and initial characterization of novel prion protein gene (Frontiers in veterinary science · 2026Article
- Spatial and Temporal Patterns of Prion Gene Variation Are Consistent With a Response to Chronic Wasting Disease-Induced Selection in Wild White-Tailed Deer.Ecology and evolution · 2025Article
- Review
- The Strain Properties of Korean and North American Chronic Wasting Disease Prions Are Indistinguishable.The Journal of infectious diseases · 2025Article
- Effect of primary structural variation on cervid prion protein in flexibility, stability, and spontaneous misfolding propensity.Neurobiology of disease · 2025Article
- Overview of North American Isolates of Chronic Wasting Disease Used for Strain Research.Pathogens (Basel, Switzerland) · 2025Review
- The Evolution of Experimental Rodent Models for Prion Diseases.Journal of neurochemistry · 2025Review
- Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Scrapie versus Chronic Wasting Disease in White-Tailed Deer.Emerging infectious diseases · 2024Article
- New developments in prion disease research using genetically modified mouse models.Cell and tissue research · 2023Review
- Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland.Emerging infectious diseases · 2023Article
- Review
- Article
- Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae.Veterinary research · 2021Review
- Chronic Wasting Disease Transmission Risk Assessment for Farmed Cervids in Minnesota and Wisconsin.Viruses · 2021Article
- Spatio-temporal analyses reveal infectious disease-driven selection in a free-ranging ungulate.Royal Society open science · 2021Article
- New and distinct chronic wasting disease strains associated with cervid polymorphism at codon 116 of the Prnp gene.PLoS pathogens · 2021Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Understanding the molecular parameters governing prion propagation is crucial for controlling these lethal, proteinaceous, and infectious neurodegenerative diseases. To explore the effects of prion protein (PrP) sequence and structural variations on intra- and interspecies transmission, we integrated studies in deer, a species naturally susceptible to chronic wasting disease (CWD), a burgeoning, contagious epidemic of uncertain origin and zoonotic potential, with structural and transgenic (Tg) mouse modeling and cell-free prion amplification. CWD properties were faithfully maintained in deer following passage through Tg mice expressing cognate PrP, and the influences of naturally occurring PrP polymorphisms on CWD susceptibility were accurately reproduced in Tg mice or cell-free systems. Although Tg mice also recapitulated susceptibility of deer to sheep prions, polymorphisms that provided protection against CWD had distinct and varied influences. Whereas substitutions at residues 95 and 96 in the unstructured region affected CWD propagation, their protective effects were overridden during replication of sheep prions in Tg mice and, in the case of residue 96, deer. The inhibitory effects on sheep prions of glutamate at residue 226 in elk PrP, compared with glutamine in deer PrP, and the protective effects of the phenylalanine for serine substitution at the adjacent residue 225, coincided with structural rearrangements in the globular domain affecting interaction between α-helix 3 and the loop between β2 and α-helix 2. These structure-function analyses are consistent with previous structural investigations and confirm a role for plasticity of this tertiary structural epitope in the control of PrP conversion and strain propagation.
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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.