Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.

PrP(C), a host protein which in prion-infected animals is converted to PrP(Sc), is linked to the cell membrane by a GPI anchor. Mice expressing PrP(C) without GPI anchor (tgGPI⁻ mice), are susceptible to prion infection but accumulate anchorless PrP(Sc) extra-, rather than intracellularly. We invest...

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Autores principales:	Sukhvir Paul Mahal, Joseph Jablonski, Irena Suponitsky-Kroyter, Anja Maria Oelschlegel, Maria Eugenia Herva, Michael Oldstone, Charles Weissmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f3576846260f4508b2f70776e10df08b
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spelling	oai:doaj.org-article:f3576846260f4508b2f70776e10df08b2021-11-18T06:04:20ZPropagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.1553-73661553-737410.1371/journal.ppat.1002746https://doaj.org/article/f3576846260f4508b2f70776e10df08b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22685404/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374PrP(C), a host protein which in prion-infected animals is converted to PrP(Sc), is linked to the cell membrane by a GPI anchor. Mice expressing PrP(C) without GPI anchor (tgGPI⁻ mice), are susceptible to prion infection but accumulate anchorless PrP(Sc) extra-, rather than intracellularly. We investigated whether tgGPI⁻ mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrP(Sc). We found that RML and ME7, but not 22L prions propagated in tgGPI⁻ brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrP(Sc) (PrP(res)) in RML- or ME7-infected tgGPI⁻ brain were 25-50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrP(Sc) and SFL PrP(Sc) are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI⁻ mice.Sukhvir Paul MahalJoseph JablonskiIrena Suponitsky-KroyterAnja Maria OelschlegelMaria Eugenia HervaMichael OldstoneCharles WeissmannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002746 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sukhvir Paul Mahal Joseph Jablonski Irena Suponitsky-Kroyter Anja Maria Oelschlegel Maria Eugenia Herva Michael Oldstone Charles Weissmann Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
description	PrP(C), a host protein which in prion-infected animals is converted to PrP(Sc), is linked to the cell membrane by a GPI anchor. Mice expressing PrP(C) without GPI anchor (tgGPI⁻ mice), are susceptible to prion infection but accumulate anchorless PrP(Sc) extra-, rather than intracellularly. We investigated whether tgGPI⁻ mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrP(Sc). We found that RML and ME7, but not 22L prions propagated in tgGPI⁻ brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrP(Sc) (PrP(res)) in RML- or ME7-infected tgGPI⁻ brain were 25-50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrP(Sc) and SFL PrP(Sc) are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI⁻ mice.
format	article
author	Sukhvir Paul Mahal Joseph Jablonski Irena Suponitsky-Kroyter Anja Maria Oelschlegel Maria Eugenia Herva Michael Oldstone Charles Weissmann
author_facet	Sukhvir Paul Mahal Joseph Jablonski Irena Suponitsky-Kroyter Anja Maria Oelschlegel Maria Eugenia Herva Michael Oldstone Charles Weissmann
author_sort	Sukhvir Paul Mahal
title	Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
title_short	Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
title_full	Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
title_fullStr	Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
title_full_unstemmed	Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
title_sort	propagation of rml prions in mice expressing prp devoid of gpi anchor leads to formation of a novel, stable prion strain.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f3576846260f4508b2f70776e10df08b
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Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.

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