Comparative titration of experimental ovine BSE infectivity in sheep and mice

Titration studies of the infectivity of experimental bovine spongiform encephalopathy (BSE) in sheep are necessary to assess the risk for human health posed by the ovine infection relative to the original cattle disease. Here, a comparative titration was performed of sheep-passaged BSE infectivity in Romney sheep and RIII mice, by the intracerebral (i.c.) and i.c. plus intraperitoneal (i.p.) routes, respectively. The sheep-to-mouse species barrier was lower than anticipated, as similar titres were obtained for both sheep [1 x 10(5.4) (i.c.) ID(50) g(-1))] and mice [1 x 10(5.0) (i.c.+i.p.) ID(50) g(-1)]. Moreover, sheep of the ARR/ARR PrP genotype all succumbed to i.c. challenge with a 10(-3) dilution of 0.5 g of a brainstem pool from BSE-affected sheep, indicating that resistance to natural infection in sheep of this genotype must reside in some mechanism of peripheral pathogenesis.