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Journal of Virology, June 2009, p. 5321-5328, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02502-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prion Protein Glycosylation Is Not Required for Strain-Specific Neurotropism{triangledown} ,{dagger}

Justin R. Piro,1 Brent T. Harris,2 Koren Nishina,1 Claudio Soto,3 Rodrigo Morales,3 Judy R. Rees,4 and Surachai Supattapone1,5*

Departments of Biochemistry,1 Pathology,2 Community and Family Medicine (Biostatistics and Epidemiology),4 Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755,5 Department of Neurology, University of Texas Medical School, Houston, Texas 770303

Received 5 December 2008/ Accepted 9 March 2009

In this study, we tested the hypothesis that the glycosylation of the pathogenic isoform of the prion protein (PrPSc) might encode the selective neurotropism of prion strains. We prepared unglycosylated cellular prion protein (PrPC) substrate molecules from normal mouse brain by treatment with PNGase F and used reconstituted serial protein cyclic misfolding amplification reactions to produce RML and 301C mouse prions containing unglycosylated PrPSc molecules. Both RML- and 301C-derived prions containing unglycosylated PrPSc molecules were infectious to wild-type mice, and neuropathological analysis showed that mice inoculated with these samples maintained strain-specific patterns of PrPSc deposition and neuronal vacuolation. These results show that PrPSc glycosylation is not necessary for strain-dependent prion neurotropism.


* Corresponding author. Mailing address: Department of Biochemistry, 7200 Vail Building, Dartmouth Medical School, Hanover, NH 03755. Phone: (603) 650-1192. Fax: (603) 650-1193. E-mail: supattapone{at}dartmouth.edu

{triangledown} Published ahead of print on 18 March 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, June 2009, p. 5321-5328, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02502-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.