Evidence map›Paper›PMID 30908557›Full record

ArticlePLoS pathogens2019

Full restoration of specific infectivity and strain properties from pure mammalian prion protein.

Cassandra M Burke, Daniel J Walsh, Alexander D Steele, Umberto Agrimi, Michele Angelo Di Bari, Joel C Watts, Surachai Supattapone

Abstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed.

  1. Article
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  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Mechanisms of prion-induced toxicity.Cell and tissue research · 2023
    Review
  13. Review
  14. Article
  15. Review
  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Cassandra M BurkeDepartments of Biochemistry and Cell Biology at Darthmouth, Hanover, New Hampshire, United States of America.ORCID 0000-0001-7017-7926
Daniel J WalshDepartments of Biochemistry and Cell Biology at Darthmouth, Hanover, New Hampshire, United States of America.
Alexander D SteeleDepartments of Biochemistry and Cell Biology at Darthmouth, Hanover, New Hampshire, United States of America.ORCID 0000-0001-6608-8533
Umberto AgrimiDepartment of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
Michele Angelo Di BariDepartment of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.ORCID 0000-0003-0943-6823
Joel C WattsTanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-2604-2925
Surachai SupattaponeDepartments of Biochemistry and Cell Biology at Darthmouth, Hanover, New Hampshire, United States of America.ORCID 0000-0001-9060-4550

Funding

HOST-MICROBE INTERACTIONST32AI007519 · NIAID · DARTMOUTH COLLEGE · PI DEBORAH A HOGAN · 1997 to 2026
$5.9M
Structural Mechanism of Mammalian Prion InfectivityR01NS118796 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI, ZILM, KURT WILLIAM · 2020 to 2024
$2.8M
Dissecting the Mechanism of Prion Formation with a Permissive HostR01NS102301 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI · 2018 to 2021
$2.2M
Structural Mechanism of Mammalian Prion InfectivityR56NS094576 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI, ZILM, KURT WILLIAM · 2017 to 2017
$567k
Long-Term Safety, Efficacy, and Mechanism of PERK Inhibition Therapy for Prion DiseaseR21NS095763 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI · 2016 to 2017
$446k
Combination Chemotherapy for Treatment of Prion DiseaseR21NS099928 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI · 2017 to 2018
$446k
NIAID NIH HHS T32 AI007519NINDS NIH HHS R01 NS102301NINDS NIH HHS R01 NS118796NINDS NIH HHS R21 NS095763NINDS NIH HHS R21 NS099928NINDS NIH HHS R56 NS094576
6 · The paper itself

Abstract

The protein-only hypothesis predicts that infectious mammalian prions are composed solely of PrPSc, a misfolded conformer of the normal prion protein, PrPC. However, protein-only PrPSc preparations lack significant levels of prion infectivity, leading to the alternative hypothesis that cofactor molecules are required to form infectious prions. Here, we show that prions with parental strain properties and full specific infectivity can be restored from protein-only PrPSc in vitro. The restoration reaction is rapid, potent, and requires bank vole PrPC substrate, post-translational modifications, and cofactor molecules. To our knowledge, this represents the first report in which the essential properties of an infectious mammalian prion have been restored from pure PrP without adaptation. These findings provide evidence for a unified hypothesis of prion infectivity in which the global structure of protein-only PrPSc accurately stores latent infectious and strain information, but cofactor molecules control a reversible switch that unmasks biological infectivity.

Indexed as

AnimalsArvicolinaeCommunicable DiseasesMammalsPrion ProteinsPrionsProtein Processing, Post-TranslationalPrPC ProteinsPrPSc ProteinsPrion ProteinsPrionsPrPC ProteinsPrPSc Proteins

Identifiers

PMID30908557
PMCPMC6448948

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.