NR AOGO
AU Kulkarni,R.V.; Slepoy,A.; Singh,R.R.P.; Cox,D.L.; Pazmandi,F.
TI Theoretical modeling of prion disease incubation
QU Biophysical Journal 2003 Aug; 85(2): 707-18
PT evaluation studies; journal article; validation studies
AB We apply a theoretical aggregation model to laboratory and epidemiological prion disease incubation time data. In our model, slow growth of misfolded protein aggregates from small initial seeds controls the latent or lag phase; aggregate fissioning and subsequent spreading leads to an exponential growth phase. Our model accounts for the striking reproducibility of incubation times for high dose inoculation of lab animals. In particular, low dose yields broad incubation time distributions, and increasing dose narrows distributions and yields sharply defined onset times. We also explore how incubation time statistics depend upon aggregate morphology. We apply our model to fit the experimental dose-incubation curves for distinct strains of scrapie, and explain logarithmic variation at high dose and deviations from logarithmic behavior at low dose. We use this to make testable predictions for infectivity time-course experiments.
MH Animals; Cattle; Comparative Study; Computer Simulation; Hamsters; Macromolecular Systems; Mice; *Models, Biological; Models, Chemical; Neurons/chemistry/*metabolism; PrPsc Proteins/chemistry/*metabolism/*pathogenicity; Prion Diseases/epidemiology/*metabolism/*transmission; Prions/chemistry/metabolism; Protein Binding; Protein Conformation; Protein Folding; Species Specificity; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.
AD Department of Physics, University of California, Davis, California, USA. kulkarni@physics.ucdavis.edu
SP englisch
PO USA