TY - JOUR
T1 - The measured level of prion infectivity varies in a predictable way according to the aggregation state of the infectious agent
AU - Masel, Joanna
AU - Jansen, Vincent A.A.
N1 - Funding Information:
We thank Graham Jackson, Byron Caughey, Angela McLean, Hester Korthals Altes and Bob May for helpful discussions. J.M. gratefully acknowledges the support of the Rhodes Trust and V.A.A.J. the support of The Wellcome Trust grant number 051319.
PY - 2001/2/14
Y1 - 2001/2/14
N2 - Transmissible spongiform encephalopathies are believed to be caused by an infectious form of the prion protein, designated PrPSc. The concentration of PrPSc is often poorly correlated to the level of infectivity. Infectivity can be measured in two ways, namely endpoint titration and the incubation time assay, but patterns of infectivity vary depending on which method is used. These discrepancies can be explained by variation in the aggregation state of PrPSc. Both methods of measuring infectivity are modelled mathematically, and the theoretical results are in agreement with published data. It was found to be theoretically impossible to characterise prion infectivity by a multiple of a single quantity representing 'one prion', no matter how it is measured. Infectivity is instead characterised by both the number and sizes of the PrPSc aggregates. Apparent discrepancies arise when these complexities are reduced to a single number.
AB - Transmissible spongiform encephalopathies are believed to be caused by an infectious form of the prion protein, designated PrPSc. The concentration of PrPSc is often poorly correlated to the level of infectivity. Infectivity can be measured in two ways, namely endpoint titration and the incubation time assay, but patterns of infectivity vary depending on which method is used. These discrepancies can be explained by variation in the aggregation state of PrPSc. Both methods of measuring infectivity are modelled mathematically, and the theoretical results are in agreement with published data. It was found to be theoretically impossible to characterise prion infectivity by a multiple of a single quantity representing 'one prion', no matter how it is measured. Infectivity is instead characterised by both the number and sizes of the PrPSc aggregates. Apparent discrepancies arise when these complexities are reduced to a single number.
KW - Amyloid
KW - Incubation time assay
KW - Mathematical model
KW - One-hit model
KW - Prion disease
KW - Protein aggregation
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U2 - 10.1016/S0925-4439(00)00095-8
DO - 10.1016/S0925-4439(00)00095-8
M3 - Article
C2 - 11342005
AN - SCOPUS:0035857483
VL - 1535
SP - 164
EP - 173
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 2
ER -