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From: TSS ()
Subject: PrPTSE Distribution in a Primate Model of Variant, Sporadic, and Iatrogenic Creutzfeldt-Jakob Disease
Date: October 29, 2005 at 2:22 pm PST

Journal of Virology, November 2005, p. 14339-14345, Vol. 79, No. 22
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.22.14339-14345.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PrPTSE Distribution in a Primate Model of Variant, Sporadic, and Iatrogenic Creutzfeldt-Jakob Disease

Christian Herzog, Julie Rivière, Nathalie Lescoutra-Etchegaray, Aurore Charbonnier, Virginie Leblanc, Nicole Salès, Jean-Philippe Deslys, and Corinne Ida Lasmézas*
Commissariat à l'Energie Atomique, Département de Recherche Médicale, BP6, 92265 Fontenay-aux-Roses, France

Received 13 May 2005/ Accepted 25 August 2005

Human prion diseases, such as Creutzfeldt-Jakob disease (CJD), are neurodegenerative and fatal. Sporadic CJD (sCJD) can be transmitted between humans through medical procedures involving highly infected organs, such as the central nervous system. However, in variant CJD (vCJD), which is due to human contamination with the bovine spongiform encephalopathy (BSE) agent, lymphoreticular tissue also harbors the transmissible spongiform encephalopathy-associated prion protein (PrPTSE), which poses a particularly acute risk for iatrogenic transmission. Two blood transfusion-related cases are already documented. In addition, the recent observation of PrPTSE in spleen and muscle in sCJD raised the possibility that peripheral PrPTSE is not limited to vCJD cases. We aimed to clarify the peripheral pathogenesis of human TSEs by using a nonhuman primate model which mimics human diseases. A highly sensitive enzyme-linked immunosorbent assay was adapted to the detection of extraneural PrPTSE. We show that affected organs can be divided into two groups. The first is peripheral organs accumulating large amounts of PrPTSE, which represent a high risk of iatrogenic transmission. This category comprises only lymphoreticular organs in the vCJD/BSE model. The second is organs with small amounts of PrPTSE associated with nervous structures. These are the muscles, adrenal glands, and enteric nervous system in the sporadic, iatrogenic, and variant CJD models. In contrast to the first set of organs, this low level of tissue contamination is not strain restricted and seems to be linked to secondary centrifugal spread of the agent through nerves. It might represent a risk for iatrogenic transmission, formerly underestimated despite previous reports of low rates of transmission from peripheral organs of humans to nonhuman primates (5, 10). This study provides an additional experimental basis for the classification of human organs into different risk categories and a rational re-evaluation of current risk management measures.

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* Corresponding author. Present address: The Scripps Research Institute, Department of Infectology, 33458 Jupiter, FL. Phone: (561) 799-8895. Fax: (561) 799-8960. E-mail: lasmezas@scripps.edu .

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Journal of Virology, November 2005, p. 14339-14345, Vol. 79, No. 22
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.22.14339-14345.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.


http://jvi.asm.org/cgi/content/abstract/79/22/14339

TSS



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