Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice

• Published in: Emerging infectious diseases Vol. 26; no. 6; pp. 1130 - 1139
• Main Authors: Marín-Moreno, Alba, Huor, Alvina, Espinosa, Juan Carlos, Douet, Jean Yves, Aguilar-Calvo, Patricia, Aron, Naima, Píquer, Juan, Lugan, Sévérine, Lorenzo, Patricia, Tillier, Cecile, Cassard, Hervé, Andreoletti, Olivier, Torres, Juan María
• Format: Journal Article
• Language: English
• Published: United States U.S. National Center for Infectious Diseases 01-06-2020; Centers for Disease Control and Prevention
• Subjects: Adaptation; Analysis; Animal genetic engineering; atypical bovine spongiform encephalopathy; Bovine spongiform encephalopathy; Brain research; BSE; Cattle; Creutzfeldt-Jakob disease; Disease; Ethics; Experiments; Food chains; Glucose; Life Sciences; prion; Prions; Prions (Proteins); Proteins; Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice; Rodents; Sheep; Transgenic animals; transmissible spongiform encephalopathies; transmission barrier; Val129-PrP; Virulence; Zoonoses; Spain; France; Europe; BSE; transmissible spongiform encephalopathies; Creutzfeldt-Jakob disease; atypical bovine spongiform encephalopathy; transmission barrier; prion; zoonoses; CJD; Val129-PrP
• ISSN: 1080-6040; 1080-6059
• DOI: 10.3201/EID2606.181790

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet
, TgMet/Val
, and TgVal
. L-type BSE showed a higher zoonotic potential in TgMet
mice than classical BSE, whereas Val
-PrP variant was a strong molecular protector against L-type BSE prions, even in heterozygosis. H-type BSE could not be transmitted to any of the mice. We also adapted 1 H- and 1 L-type BSE isolate to sheep-PrP transgenic mice and inoculated them into human-PrP transgenic mice. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet
and TgVal
, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.