NR AUPO
AU Nonno,R.; Di Bari,M.A.; Cardone,F.; Vaccari,G.; Fazzi,P.; Dell'Omo,G.; Cartoni,C.; Ingrosso,L.; Boyle,A.; Galeno,R.; Sbriccoli,M.; Lipp,H.P.; Bruce,M.; Pocchiari,M.; Agrimi,U.
TI Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles
QU PLoS Pathogens 2006 Feb; 2(2): e12
PT journal article; research support, non-u.s. gov't
AB Transmission of prions between species is limited by the "species barrier," which hampers a full characterization of human prion strains in the mouse model. We report that the efficiency of primary transmission of prions from Creutzfeldt-Jakob disease patients to a wild rodent species, the bank vole (Clethrionomys glareolus), is comparable to that reported in transgenic mice carrying human prion protein, in spite of a low prion protein-sequence homology between man and vole. Voles infected with sporadic and genetic Creutzfeldt-Jakob disease isolates show strain-specific patterns of spongiform degeneration and pathological prion protein-deposition, and accumulate protease-resistant prion protein with biochemical properties similar to the human counterpart. Adaptation of genetic Creutzfeldt-Jakob disease isolates to voles shows little or no evidence of a transmission barrier, in contrast to the striking barriers observed during transmission of mouse, hamster, and sheep prions to voles. Our results imply that in voles there is no clear relationship between the degree of homology of the prion protein of the donor and recipient species and susceptibility, consistent with the view that the prion strain gives a major contribution to the species barrier. The vole is therefore a valuable model to study human prion diversity and, being susceptible to a range of animal prions, represents a unique tool for comparing isolates from different species.
IN Nonno et al. infizierten mit verschiedenen CJK-Isolaten Wildtyp-Rötelmäuse (Rötel- oder Waldwühlmaus, Clethrionomys glareolus) ungeachtet erheblicher Sequenzunterschiede ebenso effektiv wie Hausmäuse, welche ein menschliches Prionprotein exprimierten. Im Gegensatz zu Hausmaus, Hamster und Schaf scheint also die Rötelmaus praktisch keine Speziesbarriere gegenüber Infektionen mit menschlichen Prionen zu besitzen. Die Autoren weisen darauf hin, dass offensichtlich keine klare Beziehung zwischen der Höhe der Speziesbarriere und der Homologie der Prionproteine beider Spezies besteht. Man fand in den Rötelmäusen die auch bei den jeweiligen Spender-Patienten gefundenen Erregerstamm-spezifischen Schädigungs- und Akkumulationsmuster wieder und auch die biochemischen Eigenschaften der verschiedenen menschlichen Prionentypen blieben während der Rötelmaus-Passage erhalten.
MH Amino Acid Sequence; Animals; *Arvicolinae; Brain/pathology; Creutzfeldt-Jakob Syndrome/pathology/*transmission; *Disease Models, Animal; Disease Susceptibility; Humans; Mice; Mice, Transgenic; Molecular Sequence Data; PrPsc Proteins/*pathogenicity; Sequence Alignment; Species Specificity
AD Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanita, Viale Regina Elena, Rome, Italy.
SP englisch
PO USA