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

TL;DR

Researchers compared how chronic wasting disease from white-tailed and mule deer affects sheep, finding that mule deer CWD poses a higher risk to sheep.

Contribution

The study reveals differences in transmissibility and pathogenicity between white-tailed and mule deer CWD agents in sheep and transgenic mice.

Findings

White-tailed deer CWD had limited transmission to sheep with PrPSc detected in only 2 of 15 sheep.

Mule deer CWD showed higher transmission success in sheep and transgenic mice compared to white-tailed deer CWD.

Passage of mule deer CWD into ovinized mice resulted in 100% attack rate, indicating higher risk to sheep.

Abstract

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 clinical signs and incubation periods similar 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.

Fifteen Suffolk sheep 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 misfolded prion protein (PrPSc) accumulation.

PrPSc was detected in 2 of 15 sheep (both ARQ/ARQ sheep) in the brainstem at the level of the obex, with a mean incubation period (MIP) of 39 months. In affected sheep, the distribution of PrPSc was limited to the central nervous system (CNS). 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 PrPSc 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 PrPSc. These results were compared to those of passage of MD CWD agent from sheep (MD sheep CWD) 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 a risk to both the cervid and sheep populations.

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