NR AJHX
AU Payne,R.J.; Krakauer,D.C.
TI The spatial dynamics of prion disease
QU Proceedings of the Royal Society B: Biological Sciences 1998 Dec 7; 265(1412): 2341-6
PT journal article; review; review, tutorial
AB An important component of the latency period of the transmissible spongiform encephalopathies (prion diseases) can be attributed to delays during the propagation of the infectious prion isoform, PrPsc, through peripheral nervous tissues. A growing body of data report that the host prion protein, PrPc, is required in both peripheral and central nervous tissues for susceptibility to infection. We introduce a mathematical model, which treats the PrPsc as a mobile infectious pathogen, and show how peripheral delays can be understood in terms of the intercellular dispersal properties of the PrPsc strain, its decay rate, and its efficiency at transforming the PrPc. It has been observed that when two pathogenic strains co-infect a host, the presence of the first inoculated strain can slow down, or stop completely, the spread of the second strain. This is thought to result from a reduced concentration of host protein available for conversion by the second strain. Our model can explain the mechanisms of such interstrain competition and the time-course of the increased delay. The model provides a link between those data suggesting a role for a continuous chain of PrP-expressing tissue linking peripheral sites to the brain, and data on prion strain competition.
ZR 34
MH Animal; Human; *Models, Biological; PrPc Proteins/pathogenicity; PrPsc Proteins/pathogenicity; Prion Diseases/*transmission; Support, Non-U.S. Gov't
AD BBSRC-NERC Ecology & Behaviour Group, University of Oxford, UK. robert.payne@zoo.ox.ac.uk
SP englisch
PO England