title: 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.
authors.affiliation: Moredun Research Institute, Penicuik, Near Edinburgh EH26 0PZ, Scotland,  United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chianini
authors.forename: Natalia
authors.initials: N
authors.lastname: Fernández-Borges
authors.forename: Enric
authors.initials: E
authors.lastname: Vidal
authors.forename: Louise
authors.initials: L
authors.lastname: Gibbard
authors.forename: Belén
authors.initials: B
authors.lastname: Pintado
authors.forename: Jorge
authors.initials: J
authors.lastname: de Castro
authors.forename: Suzette A
authors.initials: SA
authors.lastname: Priola
authors.forename: Scott
authors.initials: S
authors.lastname: Hamilton
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Eaton
authors.forename: Jeanie
authors.initials: J
authors.lastname: Finlayson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Pang
authors.forename: Philip
authors.initials: P
authors.lastname: Steele
authors.forename: Hugh W
authors.initials: HW
authors.lastname: Reid
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dagleish
authors.forename: Joaquín
authors.initials: J
authors.lastname: Castilla
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D060467:Disease Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology* / Q000635:transmission*; D011328:Prions / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity*; D011489:Protein Denaturation; D017510:Protein Folding; D011817:Rabbits; D013045:Species Specificity
chemical_list: D011328:Prions; D019286:Endopeptidase K