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 ϭ 20), orally inoculated (n ϭ 19), and noninoculated (n ϭ 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 (PrP Sc ) 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, PrP Sc 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. IMPORTANCEWe 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 (PrP Sc ) 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 PrP Sc 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.

The ecology of chronic wasting disease in wildlife

“…Beyond elk, deer (red, mule, white-tailed, black-tailed), and moose populations, the role of other species in CWD maintenance has not been explored extensively. Experimental data, generally using intra-cranial inoculation (Hamir et al, 2008), reveal that rodents (voles, mice, hamsters) (Bartz et al, 1998;Raymond et al, 2007;Heisey et al, 2010;Watts et al, 2014;Orrú et al, 2015), mesocarnivores (ferrets, mink, cats) (Bartz et al, 1998;Sigurdson et al, 2008;Perrott et al, 2013), livestock (cattle, sheep, pigs) (Hamir et al, 2001(Hamir et al, , 2005(Hamir et al, , 2006Madsen-Bouterse et al, 2016;Moore et al, 2017), and other deer species (Reeve's muntjac, Muntiacus reevesi and fallow deer, Dama dama) (Hamir et al, 2011;Nalls et al, 2013) are susceptible to infectious CWD prions. In vitro and in vivo models have produced mixed results regarding the ability of CWD to cross the species barrier into humans and livestock.…”

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

“…Given the resilience of the infectious prion [23], the relative ease of transmission [24], and the uncertain interspecific barrier to transmission [25–27], a response plan is necessary as more is learned about the health and economic impacts of CWD. Therefore, management has primarily focused on containment utilizing various combinations of expanded surveillance, restrictions on movement or translocation of susceptible individuals, public hunting, and culling by government agencies [4,28–31].…”

TSE Monitoring in Wildlife Epidemiology, Transmission, Diagnosis, Genetics and Control

“…There are other animals that can experimentally be infected, both cervid and noncervid species. The experimental host range includes squirrel monkey [82,83], several species of voles [84,85], white-footed mice [29], Syrian golden hamsters [86], ferrets [87], raccoons [88], cats [89], pigs [90], and sheep [91]. Other cervids are susceptible to experimental CWD infection: fallow deer (Dama dama) [92] and muntjac deer (Muntiacus reevesi) [93].…”