Abstract Chronic wasting disease is a fatal transmissible prion condition of free-ranging and farmed cervids including deer, elk, moose, muntjac and reindeer. Prionemia is a pathogenic feature of chronic wasting disease in cervids and underpins development of an ante-mortem blood test for effective disease management. To help achieve this goal, we show here that cervid PrP transgenic Drosophila can detect prion-infected blood from cervids with chronic wasting disease. We first established that cervid PrP Drosophila were highly sensitive to cervid prions since these flies were responsive to dilutions in the range of 10 − 2 to ≥ 10 − 10 of brain homogenate from terminal chronic wasting disease-affected cervids. We subsequently showed cervid PrP Drosophila developed a neurotoxic phenotype, evidenced by accelerated loss of locomotor activity and survival, after exposure to blood from cervids with experimental or natural chronic wasting disease. Cervid PrP Drosophila were sensitive to whole blood and blood fractions including plasma, buffy coat and different leukocyte subsets isolated from prion disease-affected cervids. Importantly, we showed that cervid PrP Drosophila were sensitive to blood samples isolated from chronic wasting disease-affected cervids during the pre-clinical phase of the condition. Significantly, we demonstrated that the neurotoxic fly phenotype which developed after exposure to prion-infected cervid blood was transmissible but was not associated with the accumulation of RT-QuIC-detectable prion seeding activity, which does occur after exposure to brain-derived cervid prions. Our data show that cervid PrP Drosophila can successfully detect blood from CWD-affected cervids and indicate that blood-borne prions have distinct propagation properties in PrP transgenic Drosophila compared to brain-derived prions.
Thackray et al. (Wed,) studied this question.