title: Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties.
abstract: The agents responsible for transmissible spongiform encephalopathies (TSEs), or prion diseases, contain as a major component PrP(Sc), an abnormal conformer of the host glycoprotein PrP(C). TSE agents are distinguished by differences in phenotypic properties in the host, which nevertheless can contain PrP(Sc) with the same amino-acid sequence. If PrP alone carries information defining strain properties, these must be encoded by post-translational events. Here we investigated whether the glycosylation status of host PrP affects TSE strain characteristics. We inoculated wild-type mice with three TSE strains passaged through transgenic mice with PrP devoid of glycans at the first, second or both N-glycosylation sites. We compared the infectious properties of the emerging isolates with TSE strains passaged in wild-type mice by in vivo strain typing and by the standard scrapie cell assay in vitro. Strain-specific characteristics of the 79A TSE strain changed when PrP(Sc) was devoid of one or both glycans. Thus infectious properties of a TSE strain can be altered by post-translational changes to PrP which we propose result in the selection of mutant TSE strains.
authors: Division of Neurobiology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Enrico
authors: E
authors: Cancellotti
authors: Sukhvir P
authors: SP
authors: Mahal
authors: Robert
authors: R
authors: Somerville
authors: Abigail
authors: A
authors: Diack
authors: Deborah
authors: D
authors: Brown
authors: Pedro
authors: P
authors: Piccardo
authors: Charles
authors: C
authors: Weissmann
authors: Jean C
authors: JC
authors: Manson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D006031:Glycosylation; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011134:Polysaccharides / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017096:Prion Diseases / Q000378:metabolism / Q000635:transmission* / Q000821:virology; D011499:Protein Processing, Post-Translational; D014779:Virus Replication
chemical_list: D011134:Polysaccharides; D018620:PrPSc Proteins
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