The diversity of strains of ovine
prions within classical
scrapie isolates was investigated by transmission studies in wild type mice. To determine the maximum diversity of
prion strains present in each ovine
scrapie isolate examined, isolates from mice having the shortest and longest incubation times for terminal disease after primary inoculation were passaged serially. Serial passage of ARQ/ARQ
scrapie isolates in RIII mice revealed the ME7
prion strain in mice with short incubation times for terminal
prion disease and the 87A strain in those mice with long incubation times. Serial passage of VRQ/VRQ
scrapie isolates in RIII mice led to emergence of the 221C
prion strain in mice with short incubation times and a variant of the 221C strain in those mice with long incubation times. RIII mice with short incubation times had higher levels of total and
proteinase K-resistant PrP(Sc) compared with those RIII mice with long incubation times, while mice with long incubation times had large aggregates and plaques of PrP(Sc). ME7 PrP(Sc) differed in stability compared with the 87A
prion strain, while PrP(Sc) associated with 221C had similar stability to that of the 221C variant. Serial passage in VM mice led to identification of ME7 and 87V in the same
scrapie isolate. The data show that different
prion strains can emerge from the same ovine
scrapie isolate following serial passage in wild type mice and that the transmission properties of these strains correlate with distinct patterns of PrP(Sc) deposition.