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From: TSS ()
Subject: Prion Infection of Muscle Cells In Vitro
Date: April 12, 2007 at 10:58 am PST

Journal of Virology, May 2007, p. 4615-4624, Vol. 81, No. 9
0022-538X/07/$08.00+0 doi:10.1128/JVI.02628-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prion Infection of Muscle Cells In Vitro
Wendy M. Dlakic, Eric Grigg, and Richard A. Bessen*
Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 59717

Received 28 November 2006/ Accepted 9 February 2007

The prion agent has been detected in skeletal muscle of humans and animals with prion diseases. Here we report scrapie infection of murine C2C12 myoblasts and myotubes in vitro following coculture with a scrapie-infected murine neuroblastoma (N2A) cell line but not following incubation with a scrapie-infected nonneuronal cell line or a scrapie brain homogenate. Terminal differentiation of scrapie-infected C2C12 myoblasts into myotubes resulted in an increase in the expression of the disease-specific prion protein, PrPSc. The amount of scrapie infectivity or PrPSc in C2C12 myotubes was comparable to the levels found in scrapie-infected N2A cells, indicating that a high level of infection was established in muscle cells. Subclones of scrapie-infected C2C12 cells produced high levels of PrPSc in myotubes, and the C-terminal C2 polypeptide fragment of PrPSc was found based on deglycosylation and PrPSc-specific immunoprecipitation of cell lysates. This is the first report of a stable prion infection in muscle cells in vitro and of a long-term prion infection in a nondividing, differentiated peripheral cell type in culture. These in vitro studies also suggest that in vivo prion infection of skeletal muscle requires contact with prion-infected neurons or, possibly, nerve terminals.

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* Corresponding author. Mailing address: Department of Veterinary Molecular Biology, P.O. Box 173610, Montana State University, Bozeman, MT 59717. Phone: (406) 994-1563. Fax: (406) 994-4303. E-mail: rbessen@montana.edu

Published ahead of print on 21 February 2007.

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Journal of Virology, May 2007, p. 4615-4624, Vol. 81, No. 9
0022-538X/07/$08.00+0 doi:10.1128/JVI.02628-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

http://jvi.asm.org/cgi/content/abstract/81/9/4615?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=81&issue=9&resourcetype=HWCIT


TSS



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