Chronic Wasting Disease in Bank Voles: Characterisation of the Shortest Incubation Time Model for Prion Diseases

• DOI: 10.1371/journal.ppat.1003219
• Publication Date: 2013-03-07T21:56:17Z
• Authors: Michele Angelo Di...; Romolo Nonno; Joaquín Castilla; Claudia D'Agostino; Laura Pirisinu; Geraldina Riccardi; Michela Conte; Juergen Richt; Robert Kunkle; Jan Langeveld; Gabriele Vaccari; Umberto Agrimi
• Keywords: Chronic wasting disease; Bank vole; Infectivity; Incubation period

In order to assess the susceptibility of bank voles chronic wasting disease (CWD), we inoculated carrying isoleucine or methionine at codon 109 (Bv109I and Bv109M, respectively) with CWD isolates from elk, mule deer white-tailed deer. Efficient transmission rate (100%) was observed mean survival times ranging 156 281 days post inoculation. Subsequent passages in Bv109I allowed us isolate all sources same vole-adapted strain (Bv109ICWD), typified by unprecedented short incubation 25–28 ∼35 days. Neuropathological molecular characterisation Bv109ICWD showed that classical features mammalian prion diseases were recapitulated less than one month after intracerebral characterised a mild discrete distribution spongiosis relatively low levels protease-resistant PrPSc (PrPres) brain regions. Despite PrPres time lapse available for its accumulation, end-point titration revealed brains terminally-ill contained up 108,4 i.c. ID50 infectious units per gram. efficiently replicated protein misfolding cyclic amplification (PMCA) infectivity faithfully generated vitro, as demonstrated preservation peculiar on re-isolation Bv109I. Overall, provide evidence isolated three-cervid species. unique characteristics "virulence", accumulation high infectivity, thus providing exceptional opportunities improve basic knowledge relationship between PrPSc, neurodegeneration infectivity.