Prion Protein Amino Acid Determinants of Differential Susceptibility and Molecular Feature of Prion Strains in Mice and Voles

PLoS Pathogens

Giovanni Di Guardo¹  Umberto Agrimi²  Barbara Chiappini²  Gabriele Vaccari²  Elena Esposito²  Michele Angelo Di Bari²  Michela Conte²  Romolo Nonno²  Giacomo Dell'Omo³  Hans-Peter Lipp³  Otto Windl⁴ 

[1] Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy;Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy;Institute of Anatomy and Center for Neuroscience, University of Zürich, Zürich, Switzerland;Veterinary Laboratory Agency, TSE Molecular Biology Department, Weybridge, New Haw, Addlestone, Surrey, United Kingdom

关键词: Voles;    Scrapie;    Rodents;    Animal prion diseases;    Mouse models;    Sheep;    Hamsters;    Mice;   

DOI  :  10.1371/journal.ppat.1000113

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. At first, we found a differential susceptibility of bank and field voles compared to C57Bl/6 and wood mice. Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features. Infection with mouse-adapted scrapie 139A was faster in voles than in C57Bl/6 and wood mice. Moreover, a glycoprofile change was observed in voles, which was reverted upon back passage to mice. All strains replicated much faster in voles than in mice after adapting to the new species. PrP sequence comparison indicated a correlation between the transmission patterns and amino acids at positions 154 and 169 (Y and S in mice, N and N in voles). This correlation was confirmed when inoculating three additional rodent species: gerbils, spiny mice and oldfield mice with sheep scrapie and 139A. These rodents were chosen because oldfield mice do have the 154N and 169N substitutions, whereas gerbil and spiny mice do not have them. Our results suggest that PrP residues 154 and 169 drive the susceptibility, molecular phenotype and replication rate of prion strains in rodents. This might have implications for the assessment of host range and molecular traceability of prion strains, as well as for the development of improved animal models for prion diseases.

【 授权许可】

CC BY