Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation

Authors: MOORE, SARAH - Orise Fellow; WEST GREENLEE, M - Iowa State University; KONDRU, NAVEEN - Iowa State University; MANNE, SIREESHA - Iowa State University; Smith, Jodi; Kunkle, Robert; KANTHASAMY, ANUMANTHA - Iowa State University; Greenlee, Justin

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/6/2017
Publication Date: 9/12/2017
Citation: Moore, S.J., West Greenlee, M.H., Kondru, N., Manne, S., Smith, J.D., Kunkle, R.A., Kanthasamy, A., Greenlee, J.J. 2017. Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation. Journal of Virology. 91(19):e00926-17. https://doi.org/10.1128/JVI.00926-17.

Interpretive Summary: Chronic wasting disease (CWD) is a fatal disease of wild and captive deer and elk that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Whether CWD can transmit to swine is unknown. This study evaluated the potential of pigs to develop CWD after either intracranial or oral inoculation. Our data indicates that swine do accumulate the abnormal prion protein associated with CWD after intracranial or oral inoculation. Further, there was evidence of abnormal prion protein accumulation in lymph nodes. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. This information is useful to wildlife managers and individuals in the swine and captive cervid industries. These findings could impact future regulations for the disposal of offal from deer and elk slaughtered in commercial operations. U.S. regulators should carefully consider the new information from this study before relaxing feed ban standards designed to control potentially feed borne prion diseases.

Technical Abstract: Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of chronic wasting disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following oral or intracranial experimental inoculation. Crossbred piglets were assigned to one of three groups: intracranially inoculated (n=20), orally inoculated (n=19), or non-inoculated (n=9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by western blotting (WB), antigen-capture immunoassay (EIA), immunohistochemistry (IHC) and in vitro real-time quaking induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC and/or WB. Using RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from pigs in all inoculated groups. Bioassay was positive in 4 out of 5 pigs assayed. This study demonstrates that pigs can serve as hosts for CWD, though with scant PrPSc accumulation requiring sensitive detection methods. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.