NR AOQZ
AU Campbell,S.L.; Barron,R.M.; Chapman,K.; Manson,J.C.
TI The Relationship Between PrPsc and Infectivity in Transmissible Spongiform Encephalopathy
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-15
PT Konferenz-Poster
AB
It is hypothesised that PrPsc is the infectious agent of Transmissible Spongiform Encephalopathy and is an abnormally folded form of the normal host protein, PrPc. Deposition of PrPsc is often used as a marker for TSE disease however we have produced a murine model of TSE with the 101 leucine mutation (101L) that, after inoculation with certain TSE agents, exhibits apparently no detectable PrPsc at disease endpoint. Moreover, this infected brain material can be further transmitted in homozygous 101L mice in extremely short incubation times.
We are utilising this model, as well as a conventional ME7 model of TSE, with high levels of PrPsc at disease endpoint, to investigate the correlation between infectivity and amount of PrPsc present in brain tissue. Intracerebral inoculation of brain tissue into mice has been carried out to titrate infectivity, and the amount of PrPsc in the inocula investigated both by Western blot and ELISA-based techniques. We have found high levels of infectivity in brain tissue that exhibited no PrPsc, even in concentrated samples, on Western blot.
Alternative conformations of PrP that may contribute to infectivity have also been explored. We have found no evidence of transmembrane-PrP in our models. In our transmissible model that exhibits no PrPsc, PrP appears to have a PK-sensitivity and a detergent solubility identical to that of PrPc from uninfected animals.
These experiments demonstrate that while PrPsc is indicative of TSE infection, the absence of PrPsc does not signify absence of infectivity.
The exact nature of infectivity in our TSE model is undergoing further investigation.
This work is funded by DEFRA and BBSRC.
AD Susan L. Campbell, Rona M. Barron, Jean C. Manson, Institute for Animal Health, UK; Karen Chapman, University of Edinburgh, UK
SP englisch
PO Deutschland