Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein

M K Sandberg,E A Asante,J D F Wadsworth,H Al-Doujaily,J Collinge,S Brandner,C Powell,J M Linehan,C O'Malley,M Glatzel,C J Sigurdson

doi:10.1099/vir.0.024380-0

Abstract

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.

Highlights

Chronic wasting disease (CWD) is a prion disease affecting free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose (Williams & Young, 1980, 1982; Williams, 2005; Baeten et al, 2007)
Forms, known to be susceptible to a wide range of human and other prions, are highly resistant to infection with mule deer CWD prions. These findings agree with those of others who have previously reported an inability of CWD prions to transmit disease to transgenic mice expressing human PrP 129 methionine (Kong et al, 2005; Tamguney et al, 2006) or a poor ability of human PrP to act as a substrate for CWD prions in in vitro conversion assays (Raymond et al, 2000; Kurt et al, 2009)
The transgenic mice used in our study have proven susceptibility to infection with bovine spongiform encephalopathy (BSE) prions [Hill et al, 1997; Asante et al, 2002, 2006; Wadsworth et al, 2004 (Table 1)]

Summary

Introduction

Chronic wasting disease (CWD) is a prion disease affecting free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose (Williams & Young, 1980, 1982; Williams, 2005; Baeten et al, 2007). International concern over CWD is growing as infected cervids have been reported in 14 states in North America, two Canadian provinces and in South Korea (Kim et al, 2005; Williams, 2005; Sigurdson & Aguzzi, 2007; Sigurdson, 2008). The prevalence of CWD infection can reach levels of up to 30 % in free-ranging herds in North America and up to 90 % in animals housed in CWD research facilities (Williams, 2005). Protease-resistant cervid prion protein has recently been demonstrated in an environmental water sample from a CWD endemic area (Nichols et al, 2009)

Methods

Results

Conclusion