Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice.
Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrP(Sc) deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.
Espinosa
Juan Carlos
JC
Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain.
Andréoletti
Olivier
O
Castilla
Joaquín
J
Herva
María Eugenia
ME
Morales
Mónica
M
Alamillo
Elia
E
San-Segundo
Fayna Díaz
FD
Lacroux
Caroline
C
Lugan
Séverine
S
Salguero
Francisco Javier
FJ
Langeveld
Jan
J
Torres
Juan María
JM
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism / Q000503:physiopathology / Q000635:transmission*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018620:PrPSc Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D012608:Scrapie / Q000378:metabolism / Q000503:physiopathology; D012756:Sheep; D013045:Species Specificity; D014774:Virulence
D018620:PrPSc Proteins; D011328:Prions