Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models

TLDR

Chronic wasting disease, a prion disorder of deer and elk, is widespread in North America and, with expanding cervid populations and venison consumption, may increase human exposure, yet its transmissibility to humans remains unknown. The study used transgenic mice lacking endogenous prion protein that express either elk or human prion protein to model potential cross‑species transmission. Intracerebral inoculation of elk CWD prions caused rapid infection in cervidized mice but failed to induce disease in humanized mice even after 657–756 days, demonstrating a substantial species barrier to transmission.

Abstract

Chronic wasting disease (CWD), a prion disease affecting free-ranging and captive cervids (deer and elk), is widespread in the United States and parts of Canada. The large cervid population, the popularity of venison consumption, and the apparent spread of the CWD epidemic are likely resulting in increased human exposure to CWD in the United States. Whether CWD is transmissible to humans, as has been shown for bovine spongiform encephalopathy (the prion disease of cattle), is unknown. We generated transgenic mice expressing the elk or human prion protein (PrP) in a PrP-null background. After intracerebral inoculation with elk CWD prion, two lines of “humanized” transgenic mice that are susceptible to human prions failed to develop the hallmarks of prion diseases after >657 and >756 d, respectively, whereas the “cervidized” transgenic mice became infected after 118–142 d. These data indicate that there is a substantial species barrier for transmission of elk CWD to humans.