Differences between the white-tailed and mule deer chronic wasting disease agents after passage through sheep

Alexis J. Frese^1,2Eric Cassmann³Jifeng Bian¹Leisa Z Mandell¹Sura Smadi^1,2M. Heather West Greenlee³Justin J Greenlee^1*

• ¹National Animal Disease Center, Agricultural Research Service (USDA), Ames, United States
• ²Oak Ridge Institute for Science and Education, Oak Ridge, United States
• ³Iowa State University of Science and Technology, Ames, United States

Chronic wasting disease (CWD) is a fatal prion disease that affects the cervid species, including white-tailed deer (WTD) (Odocoileus virginianus) and mule deer (MD) (Odocoileus hemionus). Interspecies transmission of CWD is highly variable and dependent upon multiple factors. CWD of MD is transmissible to sheep after intracranial inoculation, with similar clinical signs and incubation periods to scrapie. This study used sheep and transgenic mice to investigate the susceptibility of sheep to the CWD agent from WTD (WTD sheep CWD) when intracranially inoculated and to characterize the agent in subsequent passages. Suffolk sheep (n=15) with PRNP genotypes VRQ/ARQ, ARQ/ARQ, or ARQ/ARR were inoculated intracranially with the CWD agent from WTD. Western blots and enzyme immunoassays (EIA) were performed on brain and lymphoid tissues to analyze PrP Sc accumulation. PrP Sc was detected in 2/15 sheep in the brainstem at the level of the obex (both ARQ/ARQ sheep), with a mean incubation period of 39 months. In affected sheep, distribution of PrP Sc was limited to the central nervous system.Brain material from one positive sheep (ARQ/ARQ) was used to inoculate mice expressing the cervid (Tg12) and ovine (Tg338) prion protein gene. Passage of the WTD sheep CWD agent into cervidized mice resulted in an attack rate of 83% for PrP Sc detection with a mean incubation period of 377 days for all mice, while passage into ovinized mice resulted in no clinical signs or demonstration of PrP Sc . These results were compared to the MD CWD agent from sheep (MD sheep CWD) being passed into cervidized and ovinized mice. There was an 86% attack rate in cervidized mice with a mean incubation period of 646 days for all mice and an attack rate of 100% in ovinized mice with a mean incubation period of 282 days. This data suggests that WTD CWD is unlikely to present a major risk to sheep but could be transmissible back to the cervid population. However, MD sheep CWD could present risk to both the cervid and sheep population.