This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moudjou, M. Articles by Laude, H. Search for Related Content PubMed PubMed Citation Articles by Moudjou, M. Articles by Laude, H.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 9270-9276, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9270-9276.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Glycan-Controlled Epitopes of Prion Protein Include a Major Determinant of Susceptibility to Sheep Scrapie

Mohammed Moudjou,¹ Eric Treguer,¹ Human Rezaei,¹ Elifsu Sabuncu,¹ Erdi Neuendorf,² Martin H. Groschup,² Jeanne Grosclaude,¹ and Hubert Laude^1*

Virologie Immunologie Moléculaires, INRA, Jouy-en-Josas, France,¹ Institute for Novel and Emerging Infectious Diseases, FRCVDA, Isle of Riems, Germany²

Received 17 March 2004/ Accepted 19 April 2004

A key feature of prion encephalopathies is the accumulation of a misfolded form of the host glycoprotein PrP. Cell-free and cell culture studies have shown that the efficiency of conversion of PrP into the disease-associated form is influenced by its amino acid sequence and also by its carbohydrate moiety. Here, we characterize four novel glycoform-dependent monoclonal antibodies raised against prokaryotic recombinant sheep PrP. We demonstrate that these antibodies discriminate the PrP monoglycosylated species, since two of them recognize molecules that have the first Asn glycosylation site occupied (mono1) while the other two recognize molecules glycosylated at the second site (mono2). Remarkably, the recognition of PrP by the anti-mono2 antibodies was strongly influenced by the amino acid present at position 171, i.e., either Gln or Arg. This polymorphism is known to be the main determinant of susceptibility and resistance to scrapie in sheep. Altogether, our findings lead us to propose that each glycan chain controls the accessibility of PrP determinants located close upstream from their attachment site. The monoglycoform-assigned and the allotype-restricted antibodies described here, the first to date, should provide further opportunities to investigate the involvement of each glycan chain in PrP conversion in relation to prion strain diversity and the basis of the resistance conferred by the Arg-171 amino acid.

---

* Corresponding author. Mailing address: Virologie Immunologie Moléculaires, INRA, 78352 Jouy-en-Josas Cedex, France. Phone: 331 3465 2600. Fax: 331 3465 2621. E-mail: laude{at}jouy.inra.fr.

This article is dedicated to the memory of E. Treguer, who died in August 2003.

---

Journal of Virology, September 2004, p. 9270-9276, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9270-9276.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• McKay, J. T., Brigner, T. A., Caplin, B. E., McCurdy, K. S., Forde, R. L. (2008). A real-time polymerase chain reaction assay to detect single nucleotide polymorphisms at codon 171 in the prion gene for the genotyping of scrapie susceptibility in sheep. jvdi 20: 209-212 [Abstract] [Full Text]  
• Barret, A., Forestier, L., Deslys, J.-P., Julien, R., Gallet, P. F. (2005). Glycosylation-related Gene Expression in Prion Diseases: PrPSc ACCUMULATION IN SCRAPIE INFECTED GT1 CELLS DEPENDS ON {beta}-1,4-LINKED GalNAc-4-SO4 HYPOSULFATION. J. Biol. Chem. 280: 10516-10523 [Abstract] [Full Text]