NR AJHY
AU Payne,R.J.; Krakauer,D.C.
TI The paradoxical dynamics of prion disease latency
QU Journal of Theoretical Biology 1998 Apr 21; 191(4): 345-52
PT journal article
AB A salient characteristic of the prion diseases - including Creutzfeldt-Jakob disease and bovine spongiform encephalopathy in cattle - is an extended asymptomatic incubation period followed by a rapid and often fatal clinical phase. We present a kinetic model of progression of infection based upon the existence of a bottleneck in the natural protein pathways within the cell. The model can reconcile the different time-scales of the pre-clinical and clinical phases, and is able to account for the dependency of the duration of the incubation period on several important governing factors, including the inoculum size, the phenotype of the host, and the phenotype of the pathogenic form of the prion protein. Our results suggest that saturation events - first of the rate of pathogenic transformation (an auto-catalysis ceiling), and subsequently of the bottleneck in the protein pathways - could be fundamental in determining the dynamics of infection.
MH Genetic Predisposition to Disease; Human; Models, Biological; Phenotype; PrPsc Proteins/*metabolism; Prion Diseases/*etiology/genetics/metabolism; Receptors, Cell Surface/metabolism; Support, Non-U.S. Gov't
AD Department of Zoology, University of Oxford, U.K. robert.payne@zoo.ox.ac.uk
SP englisch
PO England