Transmission of CJD from nasal brushings but not spinal fluid or RT-QuIC product.


Journal

Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278

Informations de publication

Date de publication:
06 2020
Historique:
received: 17 04 2020
accepted: 22 04 2020
pubmed: 17 6 2020
medline: 20 4 2021
entrez: 16 6 2020
Statut: ppublish

Résumé

The detection of prion seeding activity in CSF and olfactory mucosal brushings using real-time quaking-induced conversion assays allows highly accurate clinical diagnosis of sporadic Creutzfeldt-Jakob disease. To gauge transmission risks associated with these biospecimens and their testing, we have bioassayed prion infectivity levels in patients' brain tissue, nasal brushings, and CSF, and assessed the pathogenicity of amplified products of real-time quaking-induced conversion assays seeded with Creutzfeldt-Jakob disease prions. We obtained olfactory mucosal brushings and CSF from patients with a final diagnosis of sporadic Creutzfeldt-Jakob disease subtype MM1 (n = 3). Samples were inoculated intracerebrally into Tg66 transgenic mice that overexpress the homologous human 129M prion protein. The mice were evaluated for clinical, neuropathological, and biochemical evidence of prion infection. Patients' brain tissue at 10 Pellets from patients' olfactory mucosa brushings had ≥10,000-fold lower infectivity per unit volume than brain tissue, while CSF lacked detectable infectivity. Nonetheless, the results suggest that appropriate precautions may be warranted in surgical interventions involving the olfactory areas. The lack of pathogenic infectivity in the real-time quaking-induced conversion assay products provides evidence that the assay does not replicate biohazardous prions in vitro.

Identifiants

pubmed: 32538552
doi: 10.1002/acn3.51057
pmc: PMC7318090
doi:

Substances chimiques

Prion Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

932-944

Informations de copyright

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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Auteurs

Gregory J Raymond (GJ)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Brent Race (B)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Christina D Orrú (CD)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Lynne D Raymond (LD)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Matilde Bongianni (M)

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Michele Fiorini (M)

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Bradley R Groveman (BR)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Sergio Ferrari (S)

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Luca Sacchetto (L)

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Andrew G Hughson (AG)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

Salvatore Monaco (S)

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Maurizio Pocchiari (M)

Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.

Gianluigi Zanusso (G)

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Byron Caughey (B)

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.

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Classifications MeSH