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Trans-species amplification of PrP(CWD) and correlation with rigid loop 170N
Timothy D Kurt1, Glenn C Telling, Mark D Zabel
1Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523, USA.
Abstract:
Chronic wasting disease (CWD) is an efficiently transmitted spongiform encephalopathy of cervids. Whether CWD could represent a threat to non-cervid species remains speculative. Here we show that brain homogenates from several CWD-susceptible non-cervid species, such as ferrets and hamsters, support amplification of PrP(CWD) by sPMCA, whereas brain homogenates from CWD-resistant species, such as laboratory mice and transgenic mice expressing human PrP(C) [Tg(HuPrP) mice], do not. We also investigated whether several North American species that share the environment with cervids would support amplification of PrP(CWD) by sPMCA. Three native rodent species, including voles and field mice, supported PrP(CWD) amplification, whereas other species (e.g. prairie dog, coyote) did not. Analysis of PrP sequences suggests that an ability to support amplification of PrP(CWD) in trans-species sPMCA is correlated with the presence of asparagine at position 170 of the substrate species PrP. Serial PMCA may offer insights into species barriers to transmission of CWD.
