IHC profiling of brains from mice inoculated with different cattle-passaged scrapie sources

Introduction-To determine whether the classical BSE (C-BSE) outbreak in the UK could be related to classical scrapie (CS), cattle were inoculated with two brain pools. One brain pool was prepared from CS cases identified prior to 1975 (BP<1975) and the second consisted of CS cases detected after 1990 (BP>1990).

Objectives-To characterise the prion strain(s) that propagated in cattle challenged with the CH1641 source and study strain evolution.

Methods-Brain homogenates from cattle which were inoculated with either BP<1975 or BP>1990 were used to inoculate transgenic mice overexpressing ovine VRQ (tg338), ovine ARQ (tgShpXI) or bovine (tg110) alleles. Attack rates (AR), incubation period (IP), lesion profiles (LP), distribution of PrP^Sc types in the brain (IHC pattern) and Western blot (WB) were assessed to characterise the strains that emerged.   

Results & Discussion-Cattle inoculated with BP<1975 propagated very efficiently in all three mouse lines, and produced IP, LP and an IHC pattern which were indistinguishable from those produced by the CS source CH1641.  Cattle inoculated with BP>1990 produced more variable results. In tg338 mice the propagation was very inefficient, (AR 0-12.5%). In tgShpXI mice AR varied from 12.5-100% with variable IP (213-625 days post inoculation).  In tg110, AR was 100%.  LP, IHC patterns and WB profiles are in progress.   

Conclusion- After passage in cattle, BP<1975 produced a CH1641-compatible signature in all 3 mouse lines tested. The strain signatures that have emerged from cattle inoculated with BP>1990 are currently under investigation and second passages may be required to fully elucidate their signature.