Abstract
How susceptible pigs are to infection with sheep prions is unknown. We show, through transmission experiments in transgenic mice expressing porcine prion protein (PrP), that the susceptibility of this mouse model to bovine spongiform encephalopathy (BSE) can be enhanced after its passage in ARQ sheep, indicating that the pathogenicity of the BSE agent is modified after passage in sheep. Transgenic mice expressing porcine PrP were, nevertheless, completely resistant to infection with a broad panel of classical scrapie isolates from different sheep PrP genotypes and with different biochemical characteristics. The atypical (Nor98 like) isolate (SC-PS152) was the only scrapie isolate capable of transmission in these mice, although with a marked transmission barrier. Unexpectedly, the atypical scrapie agent appeared to undergo a strain phenotype shift upon transmission to porcine-PrP transgenic mice and acquired new strain properties, suggesting that atypical scrapie agent may exhibit different phenotypes depending on the host cellular PrP or other genetic factors.
Highlights
Transmissible spongiform encephalopathies (TSEs) are infectious diseases that affect humans and several livestock species, causing fatal neurodegeneration
Susceptibility and resistance to TSE infection in sheep is determined by polymorphisms at prion protein (PrP) amino acid positions 136, 154, and 171; sheep have the VRQ and ARQ alleles that are most susceptible to scrapie infection [14]
Cattle bovine spongiform encephalopathy (BSE) Three isolates of different origins were used: cattleBSE1, a pool of material from 49 BSE-infected cattle brains (TSE/08/59) supplied by the Veterinary Laboratory Agency (New Haw, Addlestone, Surrey, UK); cattle-BSE2, material obtained from the brainstem of 1 cow naturally infected with BSE supplied by the same agency (RQ 225:PG1199/00); and cattle-BSE0, an isolate obtained from the brainstem of 1 cow naturally infected with BSE supplied by Institut National de la Recherche Agronomique (INRA) (Nouzilly, France)
Summary
Transmissible spongiform encephalopathies (TSEs) are infectious diseases that affect humans and several livestock species, causing fatal neurodegeneration. The experimental inoculation of pigs and transgenic mice overexpressing porcine PrP has indicated that swine are susceptible to BSE infection by the parenteral route, with a considerable transmission barrier [8,9]. BSE and Scrapie in Porcine-PrP Transgenic Mice the use of pigs as graft donors could cause concern, given a recent report of vCJD in the recipient of a porcine dura mater graft [10]. Sheep can be experimentally infected with BSE that is not distinguished from some scrapie strains showing a 19-kDa atypical proteinase K–resistant PrP (PrPres) unglycosylated band [11,12,13]. We demonstrated that BSE experimentally passaged in homozygous ARQ sheep showed enhanced infectivity (compared with cattle BSE) as determined in transgenic mice expressing bovine PrP protein [24]
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