title: Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain.
abstract: Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to be caused by only one strain, BSE-C. BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE strains by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE strain-infected cattle. Sixty percent of the inoculated Tg mice became infected after 20 to 22 months of incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE strain-infected Tg mice, but none of the Tg mice infected with prions causing a sporadic human prion disease, showed the presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE strain-infected humanized Tg mouse brains are different from those from the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation times are observed for the BASE strain-infected Tg mice. These results suggest that in humans, the BASE strain is a more virulent BSE strain and likely lymphotropic.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. pxg13@case.edu
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.forename: Mengjie
authors.initials: M
authors.lastname: Zheng
authors.forename: Cristina
authors.initials: C
authors.lastname: Casalone
authors.forename: Liuting
authors.initials: L
authors.lastname: Qing
authors.forename: Shenghai
authors.initials: S
authors.lastname: Huang
authors.forename: Bikram
authors.initials: B
authors.lastname: Chakraborty
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Fusong
authors.initials: F
authors.lastname: Chen
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.forename: Cristiano
authors.initials: C
authors.lastname: Corona
authors.forename: Francesca
authors.initials: F
authors.lastname: Martucci
authors.forename: Barbara
authors.initials: B
authors.lastname: Iulini
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Acutis
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.forename: Xinyi
authors.initials: X
authors.lastname: Li
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monaco
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zanusso
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
authors.forename: Maria
authors.initials: M
authors.lastname: Caramelli
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000302:isolation & purification*; D018570:Risk Assessment; D013154:Spleen / Q000737:chemistry
chemical_list: D011328:Prions