HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 14, 9373-9384, April 7, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/14/9373    most recent M512239200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Piening, N. Articles by Bertsch, U. Search for Related Content PubMed PubMed Citation Articles by Piening, N. Articles by Bertsch, U. Social Bookmarking                      What's this?

Conversion Efficiency of Bank Vole Prion Protein in Vitro Is Determined by Residues 155 and 170, but Does Not Correlate with the High Susceptibility of Bank Voles to Sheep Scrapie in Vivo^*

Niklas Piening, Romolo Nonno, Michele Di Bari, Stephanie Walter, Otto Windl^¶, Umberto Agrimi, Hans A. Kretzschmar, and Uwe Bertsch¹

From the Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität, Feodor-Lynen-Strasse 23, 81377 Munich, Germany, the Instituto Superiore di Sanità, 00161 Rome, Italy, and the ^¶TSE Molecular Biology Department, Veterinary Laboratories Agency, Weybridge New Haw, Addlestone Surrey KT15 3NB, United Kingdom

The misfolded infectious isoform of the prion protein (PrP^Sc) is thought to replicate in an autocatalytic manner by converting the cellular form (PrP^C) into its pathogenic folding variant. The similarity in the amino acid sequence of PrP^C and PrP^Sc influences the conversion efficiency and is considered as the major determinant for the species barrier. We performed in vitro conversion reactions on wild-type and mutated PrP^C to determine the role of the primary sequence for the high susceptibility of bank voles to scrapie. Different conversion efficiencies obtained with bank vole and mouse PrP^C in reactions with several prion strains were due to differences at amino acid residues 155 and 170. However, the conversion efficiencies obtained with mouse and vole PrP^C in reactions with sheep scrapie did not correlate with the susceptibility of the respective species to this prion strain. This discrepancy between in vitro and in vivo data may indicate that at least in the case of scrapie transmission to bank voles additional host factors can strongly modulate the species barrier. Furthermore, in vitro conversion reactions with different prion strains revealed that the degree of alteration of the conversion efficiency induced by amino acid exchanges was varying according to the prion strain. These results support the assumption that the repertoire of conformations adopted by a certain PrP^C primary sequence is decisive for its convertibility to the strain-specific PrP^Sc conformation.

Received for publication, November 14, 2005 , and in revised form, December 22, 2005.

^* This work was supported by the European Union (EuroVolTE, Grant QLRI-CT-2002-81333). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 49-89-2180-78026; Fax: 49-89-2180-78037; E-mail: Uwe.Bertsch{at}med.uni-muenchen.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. A. Di Bari, F. Chianini, G. Vaccari, E. Esposito, M. Conte, S. L. Eaton, S. Hamilton, J. Finlayson, P. J. Steele, M. P. Dagleish, et al. The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie J. Gen. Virol., December 1, 2008; 89(12): 2975 - 2985. [Abstract] [Full Text] [PDF]

				M.-P. Courageot, N. Daude, R. Nonno, S. Paquet, M. A. Di Bari, A. Le Dur, J. Chapuis, A. F. Hill, U. Agrimi, H. Laude, et al. A cell line infectible by prion strains from different species J. Gen. Virol., January 1, 2008; 89(1): 341 - 347. [Abstract] [Full Text] [PDF]

				G. Vaccari, C. D'Agostino, R. Nonno, F. Rosone, M. Conte, M. A. Di Bari, B. Chiappini, E. Esposito, L. De Grossi, F. Giordani, et al. Prion Protein Alleles Showing a Protective Effect on the Susceptibility of Sheep to Scrapie and Bovine Spongiform Encephalopathy J. Virol., July 1, 2007; 81(13): 7306 - 7309. [Abstract] [Full Text] [PDF]

				L. Kirby, W. Goldmann, F. Houston, A. C. Gill, and J. C. Manson A novel, resistance-linked ovine PrP variant and its equivalent mouse variant modulate the in vitro cell-free conversion of rPrP to PrPres J. Gen. Virol., December 1, 2006; 87(12): 3747 - 3751. [Abstract] [Full Text] [PDF]