A substantial species barrier prevents chronic wasting disease (CWD), a cervid prion disease with unknown zoonotic potential, from being transmitted to humans, new NIH data suggested.
Healthy human cerebral organoids exposed to high concentrations of CWD inocula from white-tailed deer, mule deer, and elk for 7 days remained uninfected with CWD for up to 6 months, reported Cathryn Haigh, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID) and Rocky Mountain Laboratories in Hamilton, Montana, and co-authors in Emerging Infectious Diseases.
Another prion disease, bovine spongiform encephalopathy, has transmitted to humans and caused the emergence of variant Creutzfeldt-Jakob disease (CJD), which is widely thought to occur by eating contaminated food. Cases of CJD have risen recently in the U.S. and are universally fatal.
Recently, questions about whether CWD prions could infect humans have emerged. Last month at the American Academy of Neurology annual meeting, researchers from UT Health San Antonio led by Sarah Horn, MD, presented the case of a 72-year-old man with a history of consuming meat from a CWD-infected deer population, who had rapid-onset confusion and aggression. The man’s friend, who also had eaten venison from the same deer population, had recently died of sporadic CJD.
“Based on non-human primate and mouse models, cross-species transmission of CJD is plausible,” Horn and colleagues noted, adding that “without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases.”
To date, there is no strong evidence that CWD infects people, according to the CDC. As of February, the condition has been reported in deer, elk, and other animals in at least 32 U.S. states and four Canadian provinces.
CWD is the most transmissible of the prion disease family with highly efficient transmission between cervids. Long-term studies showed no evidence of transmission to macaques using highly sensitive prion disease-screening assays, but identified possible susceptibility in squirrel monkeys.
To test whether CWD could infect human neural tissue, the NIAID researchers used human cerebral organoids with two different prion genotypes, one of which had previously been shown to be susceptible to zoonotic prion disease. In 2022 and 2023, the team exposed organoids from both genotypes to high concentrations of CWD inocula from three different sources for 7 days and screened periodically for infection for up to 6 months.
No new CWD propagation or deposition of protease-resistant forms of human prions were seen in the CWD-exposed organoids. “Some persistence of the original inoculum was detected, which was equivalent in prion gene knockout organoids and thus not attributable to human prion propagation,” the researchers observed.
The findings show that, despite exposure to CWD prions with high infectivity and the capacity to readily become infected with CJD prions, human cerebral organoids were not capable of propagating CWD prions, Haigh and co-authors noted.
This unsuccessful propagation supports a strong species barrier from cervids to humans, they added. “Although we cannot rule out the possibility of CWD crossing into humans, our data suggest that a significant species barrier exists, even when human brain tissue is directly exposed to high-titer CWD brain homogenate for a prolonged period,” they wrote.
Disclosures
The researchers reported no disclosures.
Primary Source
Emerging Infectious Diseases
Source Reference: Groveman BR, et al “Lack of transmission of chronic wasting disease prions to human cerebral organoids” Emerg Infect Dis 2024; DOI: 10.3201/eid3006.231568.
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