Open AccessPropagation of RML Prions in Mice Expressing PrP Devoid of GPI Anchor Leads to Formation of a Novel, Stable Prion Strain
Author(s) -
Sukhvir P. Mahal,
Joseph Jablonski,
Irena Suponitsky-Kroyter,
Anja M. Oelschlegel,
María Eugenia Herva,
Michael B. A. Oldstone,
Charles Weissmann
Publication year - 2012
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1002746
Subject(s) - strain (injury) , biology , wild type , prion protein , cell , virology , cell culture , microbiology and biotechnology , gene , genetics , pathology , anatomy , medicine , disease , mutant
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.