NR AXJY
AU Browning,S.R.; Mahal,S.P.; Baker,C.A.; Smith,E.W.; Demczyk,C.A.; Weissmann,C.
TI Discrimination of Two Prion Strains in Cell Culture at a Stage Preceding Replication
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC2.8
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB Strain-specific properties of prions are believed to be encoded by the conformation of misfolded prion protein, PrPsc. We and others have developed cell lines that are susceptible to some prions strains but not to others. The mechanism by which cells distinguish between prion strains is unknown. It has been proposed that the key issue is whether or not the PrPc of the host can readily assume the conformation of the incoming PrPsc. We have isolated several murine cell lines of different origin, in particular CAD5 and PK1, which can be efficiently and persistently infected by both RML and 22L prions. Infectivity is measured by the Scrapie Cell Assay (SCA), a sensitive, rapid and quantitative procedure carried out in cell culture. Exposure of PK1 cells to low levels of an inhibitor, SB3110, renders them resistant to infection by RML, but not by 22L prions, while CAD5 cells remain completely susceptible to both prion strains when exposed to even a tenfold higher dose of the inhibitor. Surprisingly, while SB3110 inhibits infection of PK1 cells by RML, it does not inhibit RML replication when administered once infection has been established: Chronically RML-infected PK1 cells propagate and secrete infectious prions for weeks in the presence of SB3110 at concentrations that are inhibitory to de novo infection. Our findings demonstrate that establishment of persistent prion infection proceeds in at least two distinct phases, the first comprising adsorption and probably some transport processes, which may differ for at least some prion strains and are differentially subject to inhibition by SB3110, and a second phase, namely replication, which is not affected by the inhibitor.
AD S.R. Browning, S.P. Mahal, C.A. Baker, E.W. Smith, C.A. Demczyk, C. Weissmann, Scripps Research Institute, Infectology, USA
SP englisch
PO Schottland