Efficient Transmission and Characterization of Creutzfeldt–Jakob Disease Strains in Bank Voles

PLoS Pathogens

Loredana Ingrosso¹  Roberta Galeno¹  Maurizio Pocchiari¹  Franco Cardone¹  Marco Sbriccoli¹  Gabriele Vaccari²  Claudia Cartoni²  Umberto Agrimi²  Paola Fazzi²  Michele A. Di Bari²  Romolo Nonno²  Hans-Peter Lipp³  Giacomo Dell'Omo³  Moira Bruce⁴  Aileen Boyle⁴ 

[1] Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy;Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy;Division of Neuroanatomy and Behaviour, Institute of Anatomy and Centre for Neuroscience, University of Zürich, Zürich, Switzerland;Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, United Kingdom

关键词: Voles;    Creutzfeldt-Jakob disease;    Prions;    Animal prion diseases;    Mouse models;    Veterinary diseases;    Prion diseases;    Scrapie;   

DOI  :  10.1371/journal.ppat.0020012

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY