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In order to assess the susceptibility of bank voles to chronic wasting disease (CWD), we inoculated voles carrying isoleucine or methionine at codon 109 (Bv109I and Bv109M, respectively) with CWD isolates from elk, mule deer and white-tailed deer. Efficient transmission rate (100%) was observed with mean survival times ranging from 156 to 281 days post inoculation. Subsequent passages in Bv109I allowed us to isolate from all CWD sources the same vole-adapted CWD strain (Bv 109I CWD), typified by unprecedented short incubation times of 25–28 days and survival times of ∼35 days. Neuropathological and molecular characterisation of Bv 109I CWD showed that the classical features of mammalian prion diseases were all recapitulated in less than one month after intracerebral inoculation. Bv 109I CWD was characterised by a mild and discrete distribution of spongiosis and relatively low levels of protease-resistant PrP Sc  (PrP res ) in the same brain regions. Despite the low PrP res  levels and the short time lapse available for its accumulation, end-point titration revealed that brains from terminally-ill voles contained up to 10 8,4  i.c. ID 50  infectious units per gram. Bv 109I CWD was efficiently replicated by protein misfolding cyclic amplification (PMCA) and the infectivity faithfully generated  in vitro , as demonstrated by the preservation of the peculiar Bv 109I CWD strain features on re-isolation in Bv109I. Overall, we provide evidence that the same CWD strain was isolated in Bv109I from the three-cervid species. Bv 109I CWD showed unique characteristics of “virulence”, low PrP res  accumulation and high infectivity, thus providing exceptional opportunities to improve basic knowledge of the relationship between PrP Sc , neurodegeneration and infectivity.

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