Experimental transmission of bovine spongiform encephalopathy (BSE) to cynomolgus macaques, a non-human primate.
Bovine spongiform encephalopathy (BSE) was transmitted to three macaques by intracerebral inoculation of a brain homogenate from affected cattle detected in Japan. All monkeys developed abnormal behavioral signs, such as intermittent anorexia and hyperekplexia, around 24 months after inoculation. Neuronal symptoms, such as tremor, myoclonic jerking, and paralysis, appeared 27-44 months after inoculation. These symptoms worsened and total paralysis ensued within a year after onset. The disease duration was approximately 8-12 months. Both the incubation period and the duration of disease were shortened in the secondary transmission experiment to macaques. Heavy accumulation of disease-causing conformer(s) of prion protein (PrP(Sc)), with a similar glycoform profile to the PrP(Sc) contained in the inoculum, and severe spongiform changes in the histology of the brain, confirmed the successful transmission of BSE to monkeys. Florid plaques, a characteristic histological hallmark of variant Creutzfeldt-Jakob disease, were prominent in the cerebral cortex, in which a prion antigen was detected by immunohistochemistry (IHC). PrP(Sc) was mostly confined to the central nervous system, although small amounts of PrP(Sc) accumulated in the peripheral nerves of monkeys, as detected by Western blotting (WB). Neither IHC nor WB detected PrP(Sc) in the lymphatic organs/tissues, such as the tonsils, spleen, and appendix.
The Corporation for Production and Research of Laboratory Primate, Tsukuba 305-0843, Japan.
Fumiko
F
Ono
Keiji
K
Terao
Naomi
N
Tase
Akio
A
Hiyaoka
Atsushi
A
Ohyama
Yukio
Y
Tezuka
Naomi
N
Wada
Asuka
A
Kurosawa
Yuko
Y
Sato
Minoru
M
Tobiume
Ken'ichi
K
Hagiwara
Yoshio
Y
Yamakawa
Tetsutaro
T
Sata
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000175:diagnosis / Q000473:pathology / Q000635:transmission*; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008297:Male; D018620:PrPSc Proteins / Q000378:metabolism*
D018620:PrPSc Proteins