Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles

• Published in: PLoS pathogens 2006-02, Vol.2 (2), p.e12-e12
• Main Authors: Nonno, Romolo, Di Bari, Michele A, Cardone, Franco, Vaccari, Gabriele, Fazzi, Paola, Dell'Omo, Giacomo, Cartoni, Claudia, Ingrosso, Loredana, Boyle, Aileen, Galeno, Roberta, Sbriccoli, Marco, Lipp, Hans-Peter, Bruce, Moira, Pocchiari, Maurizio, Agrimi, Umberto
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Arvicolinae; Bovine spongiform encephalopathy; Brain - pathology; BSE; Clethrionomys glareolus; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - pathology; Creutzfeldt-Jakob Syndrome - transmission; Disease Models, Animal; Disease Susceptibility; Disease transmission; Epidemiology - Public Health; Genetics/Disease Models; Genetics/Genetics of Disease; Homo (Human); Humans; Infectious Diseases; Mammals; Mice; Mice, Transgenic; Molecular Sequence Data; Neuroscience; Pathology; Prions; Proteins; PrPSc Proteins - pathogenicity; Rodents; Sequence Alignment; Species Specificity; Spongiform encephalopathies
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.0020012

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.