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Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

ABSTRACT: Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (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 postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by Western blotting (WB), antigen capture enzyme 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. By RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

SUBMITTER: Moore SJ

PROVIDER: S-EPMC5599732 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

Moore S Jo SJ West Greenlee M Heather MH Kondru Naveen N Manne Sireesha S Smith Jodi D JD Kunkle Robert A RA Kanthasamy Anumantha A Greenlee Justin J JJ

Journal of virology 20170912 19

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately ...[more]

PMID: 28701407

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Project description:Chronic wasting disease (CWD) is a fatal prion disease that can infect deer, elk, and moose. CWD was first recognized in captive deer kept in wildlife facilities in Colorado from 1967 to 1979. CWD has now been detected in 25 U.S. states, 2 Canadian provinces, South Korea, Norway, and Finland. It is currently unknown if humans are susceptible to CWD infection. Understanding the health risk from consuming meat and/or products from CWD-infected cervids is a critical human health concern. Previous research using transgenic mouse models and in vitro conversion assays suggests that a significant species barrier exists between CWD and humans. To date, reported epidemiologic studies of humans consuming cervids in areas where CWD is endemic have found no evidence to confirm CWD transmission to humans. Previously, we reported data from ongoing cross-species CWD transmission studies using two species of nonhuman primates as models. Squirrel monkeys (SM) and cynomolgus macaques (CM) were inoculated by either the intracerebral or oral route with brain homogenates from CWD-infected deer and elk containing high levels of infectivity. SM were highly susceptible to CWD infection, while CM were not. In the present study, we present new data for seven CWD-inoculated CM euthanized 11 to 13 years after CWD inoculation and eight additional uninoculated control CM. New and archival CM tissues were screened for prion infection by using the ultrasensitive real-time quaking-induced conversion (RT-QuIC) assay, immunohistochemistry, and immunoblotting. In this study, there was no clinical, pathological, or biochemical evidence suggesting that CWD was transmitted from cervids to CM.IMPORTANCE Chronic wasting disease (CWD) is a fatal prion disease found in deer, elk, and moose. Since it was first discovered in the late 1960s, CWD has now spread to at least 25 U.S. states, 2 Canadian provinces, South Korea, Norway, and Finland. Eradication of CWD from areas of endemicity is very unlikely, and additional spread will occur. As the range and prevalence of CWD increase, so will the potential for human exposure to CWD prions. It is currently unknown if CWD poses a risk to human health. However, determining this risk is critical to preventing a scenario similar to that which occurred when mad cow disease was found to be transmissible to humans. In the present study, we used cynomolgus macaque monkeys as a surrogate model for CWD transmission to humans. After 13 years, no evidence for CWD transmission to macaques was detected clinically or by using highly sensitive prion disease-screening assays.

Dataset Information

Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

Publications

Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

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