Rabbits are not resistant to prion infection

Abstract

The ability of prions to infect some species and not others is determined by the transmission barrier. This unexplained phenomenon has led to the belief that certain species were not susceptible to transmissible spongiform encephalopathies (TSEs) and therefore represented negligible risk to human health if consumed. Using the protein misfolding cyclic amplification (PMCA) technique, we were able to overcome the species barrier in rabbits, which have been classified as TSE resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in vitro with disease-related prions obtained from different species, was subjected to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded material were tested for infectivity in rabbits, with one of three intracerebrally challenged animals succumbing to disease at 766 d and displaying all of the characteristics of a TSE, thereby demonstrating that leporids are not resistant to prion infection. Material from the brain of the clinically affected rabbit containing abnormal prion protein resulted in a 100% attack rate after its inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral challenge. Despite rabbits no longer being able to be classified as resistant to TSEs, an outbreak of “mad rabbit disease” is unlikely.

Prion replication without host adaptation during interspecies transmissions

“…Even in the rare event that pathogenic horse prions are produced during infection, replication by NAPA ensures that they are paradoxically not optimized for further conversion of EqPrP C upon passage. The properties of horse PrP C therefore differ significantly from rabbit PrP C , a species incorrectly thought to be resistant to prion infection (15,36). Nonetheless, several lines of evidence confirm that our description of NAPA in TgEq is not the result of an idiosyncratic resistance of EqPrP C to support prion replication.…”

Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins

“…Formation of infectivity in PMCA reactions has since been reproduced using other TSE strains (10,25,27,38,40,50). Prolonged rounds of serial PMCA can lead to de novo formation of TSE infectivity in unseeded reactions (5,16,20), but such experiments require extreme care to exclude cross-contamination (19). A recent study showed evidence of high infectivity titers in PMCA reactions with the hyper strain of transmissible mink encephalopathy, although incubation times per infectious unit were longer than those observed for brain-derived infectivity (51).…”

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

“…This effect has been shown with CWD in ferrets (Kurt et al, 2007) and prairie voles (Kurt et al, 2011), RML (a laboratory scrapie strain) in cervid transgenic mice (Green et al, 2008), mouse scrapie in hamster (Castilla et al, 2008b), and feline spongiform encephalopathy (FSE) in bovine transgenic mice (Eiden et al, 2010). Even PrP c from dog and rabbit, species which are not susceptible to TSE under natural conditions, could be converted by using scrapie (rabbit, Chianini et al, 2012) or BSE prions as seed (rabbit and dog, Vidal et al, 2013b).…”

“…Moreover intracerebral inoculation of this de novo generated protein resulted in diseases with new disease phenotypes (Saa et al, 2006;Barria et al, 2009;Chianini et al, 2012;Wang et al, 2010Wang et al, , 2012.…”