Excretion of BSE and scrapie prions in stools from murine models

doi:10.1016/j.vetmic.2008.02.014
Copyright © 2008 Elsevier B.V. All rights reserved.
Short communication

Excretion of BSE and scrapie prions in stools from murine models

Carlos Maluquer de Motesa, Jacques Grassib, Stephanie Simonb, Maria Eugenia Hervac, Juan Maria Torresc, Marti Pumarolad and Rosina Gironesa, ,

aDepartament de Microbiologia, Universitat de Barcelona, Av. Diagonal 645, Barcelona 08028, Spain bCEA, iBiTecS, Service de Pharmacologie et d’Immunologie, bâtiment 136, CEA/Saclay, 91191 Gif sur Yvette, France cCentro de Investigación en Sanidad Animal, CISA-INIA, Crta. Algete a El Casar, sn, Valdeolmos 28130, Madrid, Spain dPRIOCAT Laboratory, CReSA, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain

Received 11 October 2007; revised 9 February 2008; accepted 26 February 2008. Available online 4 March 2008.



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Abstract

Faeces from infected animals have been suggested as a potential source of contamination and transmission of prion diseases in the environment. This work describes the development of a procedure for the detection of PrPres in stools which is based on a detergent-based extraction and immunoprecipitation (IP). The procedure was evaluated by analyzing TSE-spiked sheep and mice faeces, and proved to be specific for PrPres with sensitivities of 5–10 μg of infected brain tissue. In order to analyze the shedding of prions, we studied stools from orally inoculated mice over 4-days post-inoculation and also stools from terminally sick scrapie-infected mice. PrPres was only detected in stools shortly after the oral ingestion of TSE agents. The procedure described could be a useful tool for studying the excretion of prions and for evaluating potential environmental contamination by prions.

Keywords: Prion; Scrapie; BSE; Detection; Stool



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The Journal of Infectious Diseases 2008;198:81–89 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0015$15.00 DOI: 10.1086/588193

MAJOR ARTICLE

Transmission and Detection of Prions in Feces

Jiri G. Safar,1,2 Pierre Lessard,1 Gültekin Tamgüney,1,2 Yevgeniy Freyman,1 Camille Deering,1 Frederic Letessier,1 Stephen J. DeArmond,1,3 and Stanley B. Prusiner1,2,4

1Institute for Neurodegenerative Diseases, Departments of 2Neurology, 3Pathology, and 4Biochemistry and Biophysics, University of California, San Francisco, San Francisco

In chronic wasting disease (CWD) in cervids and in scrapie in sheep, prions appear to be transmitted horizontally. Oral exposure to prion-tainted blood, urine, saliva, and feces has been suggested as the mode of transmission of CWD and scrapie among herbivores susceptible to these prion diseases. To explore the transmission of prions through feces, uninoculated Syrian hamsters (SHas) were cohabitated with or exposed to the bedding of SHas orally infected with Sc237 prions. Incubation times of 140 days and a rate of prion infection of 80%-100% among exposed animals suggested transmission by feces, probably via coprophagy. We measured the disease-causing isoform of the prion protein (PrPSc) in feces by use of the conformation-dependent immunoassay, and we titrated the irradiated feces intracerebrally in transgenic mice that overexpressed SHa prion protein (SHaPrP). Fecal samples collected from infected SHas in the first 7 days after oral challenge harbored 60 ng/g PrPSc and prion titers of 106.6 ID50/g. Excretion of infectious prions continued at lower levels throughout the asymptomatic phase of the incubation period, most likely by the shedding of prions from infected Peyer patches. Our findings suggest that horizontal transmission of disease among herbivores may occur through the consumption of feces or foodstuff tainted with prions from feces of CWD-infected cervids and scrapie-infected sheep.

Received 9 October 2007; accepted 15 November 2007; electronically published 27 May 2008.

(See the editorial commentary by Bosque and Tyler, on pages 8-9.)

Potential conflicts of interest: none reported.

Financial support: National Institutes of Health (grants AG02132, AG010770, NS22786, and NS14069); G. Harold and Leila Y. Mathers Foundation; Sherman Fairchild Foundation.

Reprints or correspondence: Dr. Stanley B. Prusiner, 513 Parnassus Ave., HSE-774, San Francisco, CA 94143-0518 (stanley@ind.ucsf.edu).

http://www.journals.uchicago.edu/doi/abs/10.1086/588193


The Journal of Infectious Diseases 2008;198:8–9 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0004$15.00 DOI: 10.1086/588194 EDITORIAL COMMENTARY Prions' Travels-Feces and Transmission of Prion Diseases P. J. Bosque1,4 and K. L. Tyler1,2,3,5

Departments of 1Neurology, 2Medicine, and 3Microbiology, University of Colorado Health Sciences Center, 4Department of Medicine (Neurology), Denver Health Medical Center, and 5Neurology Service, Denver Veterans Affairs Medical Center, Denver, Colorado

Received 9 January 2008; accepted 9 January 2008; electronically published 27 May 2008.

(See the article by Safar et al., on pages 81-9.)

Potential conflicts of interest: The authors report that they have no conflicts of interest regarding prions and prion disease.

Reprints or correspondence: Dr. K. L. Tyler, Neurology B-182, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262 (ken.tyler@uchsc.edu).

http://www.journals.uchicago.edu/doi/abs/10.1086/588194


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