Is there a risk of transmission of the CWD agent to non-cervid species

Authors: Greenlee, Justin

Submitted to: North American Deer Farmer
Publication Type: Trade Journal
Publication Acceptance Date: 9/20/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Our research group at the National Animal Disease Center has dedicated significant resources to investigating the potential of the chronic wasting disease (CWD) agent to transmit to non-cervid species. In instances where transmission occurred, we have demonstrated how to differentiate it from other prion diseases such as scrapie in sheep or bovine spongiform encephalopathy (BSE) in cattle. The species barrier is an important concept to understanding when it comes to potential interspecies transmission events of prion diseases. The species barrier describes a barrier to transmission between mammalian species and depends largely on differences in the primary structure between the prion proteins of the donor inoculum and the new host. The species barrier can result in prolonged incubation periods or a reduced proportion of animals that develop disease (attack rate). In some cases, when a prion agent does infect a new species, there is adaptation upon second passage resulting in faster incubation periods and higher attack rates. Many of our studies use the intracranial inoculation route with high titers of infectious material. The intention of this work is to test the worst-case scenario- is transmission possible under very high exposures? Positive results in this type of experiment show that transmission could be possible, but for various reasons described below results obtained from cattle, goats, and sheep suggest that transmission of CWD under farm or range conditions is unlikely. Some species, such as sheep, have prion protein polymorphisms (amino acid substitutions at specific amino acid locations in the prion protein) that can affect susceptibility to prion disease. For example, wild type sheep that are susceptible to sheep scrapie have the amino acid glutamine (Q) at codon 171 of their prion protein. Other sheep that have an arginine (R) are highly resistant to scrapie. The abnormal prion protein still enters the body of resistant (R171) sheep when they are exposed, but it fails to amplify. White-tailed deer also have prion protein polymorphisms, but less is known as to whether there is a single amino acid difference (or combination of differences) that may lend resistance to CWD. Studies are underway at the NADC to examine the CWD susceptibility of various polymorphic variants after exposure to the CWD agent through an infected pen mate. We reported on this at the 2023 NADeFA Annual Conference and will continue to make updates as new results are obtained. Previous work in sheep tells us that transmission after exposure by the oral route is more likely when the results of intracranial inoculation experiments with the same inoculum demonstrate accumulation of abnormal prion protein in lymphoid tissues (spleen, lymph nodes, tonsil). We have experimentally exposed sheep to CWD isolates from white-tailed deer, elk, and mule deer. Even using intracranial inoculations, the attack rate of CWD from white-tailed deer is low and abnormal prion protein is not detected outside of the brain and spinal cord (no accumulation in lymphoid tissues). Upon second passage of material from the IC study all sheep remained negative when tested at 96 months post-inoculation. An unexpected outcome after exposing sheep to white-tailed deer CWD prions by the oronasal route was evidence of abnormal prion protein in the tonsil and retropharyngeal lymph node of a single sheep without clinical signs when the experiment was ended after 60 months of incubation. Because of the presence of abnormal prion protein in lymphoid tissues, we expected that a second passage would result in adaptation to sheep (wide tissue distribution and high attack rate). However, the sheep from a second passage of the oronasal study have no evidence of infection after 48 months of incubation, but we plan to keep these sheep under observation for up to an additional 48 months. CW