Sheep are susceptible to the agent of transmissible mink encephalopathy after intracranial inoculation

Authors: CASSMAN, E - Iowa State University; MOORE, S - Orise Fellow; SMITH, J - Iowa State University; Greenlee, Justin

Submitted to: American Association of Veterinary Laboratory Diagnosticians
Publication Type: Abstract Only
Publication Acceptance Date: 7/20/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases caused by an infectious protein (prion). Naturally occurring prion diseases include bovine spongiform encephalopathy (BSE), scrapie in small ruminants, chronic wasting disease in cervids, transmissible mink encephalopathy (TME), Creutzfeldt-Jakob disease (CJD) in humans, and camel prion disease. An epizootic of BSE in the UK revealed the zoonotic potential of prion diseases when variant-CJD arose in people who had consumed products from cattle infected with classical BSE (C-BSE). Spontaneously arising cases of atypical BSE (L-BSE and H-BSE ) with molecular phenotypes distinct from C-BSE were first recognized in 2004. The origin of C-BSE is unknown, but evidence shows BSE infected carcasses rendered for cattle feed amplified the outbreak. The emergence of C-BSE-like strains after serial passage of H-BSE in mice have been demonstrated. One hypothesis for the origin of C-BSE is its emergence after multi-species transmission of a food-borne atypical BSE. TME has been described as a food-borne TSE; evidence suggests that TME may have originated from feeding TSE-affected downer cows to mink. Experimental transmission of TME in cattle produces molecular phenotype on western blot very similar to L-BSE. Since the emergence of C-BSE could be due to cross-species transmission and adaptability, we investigated the susceptibility and disease phenotype of bovine passaged TME (3x) inoculated into sheep. We inoculated sheep with brain homogenate from cattle clinically ill with TME: 17 intracerebral (IC) and 12 oronasal (ON). Sheep inoculated ON did not develop clinical disease and PrPSc was not detected. In the IC group, 15/17 sheep developed spongiform encephalopathy and PrPSc within the CNS detected by ELISA and IHC. Several sheep had PrPSc in neuromuscular spindles, and one sheep had PrPSc in the myenteric plexus of the small intestine. No sheep had lymphoreticular (LR) PrPSc. Two sheep died early due to intercurrent disease; they did not have detectable PrPSc by ELISA, western blot, or IHC. Non-CNS PrPSc tissue distribution is mostly host dependent. The absence of LR PrPSc in sheep is a uncommon finding. Sheep tend to accumulate PrPSc in LR tissue independent of the TSE type and route. Contrariwise, our findings demonstrate that bovine adapted TME causes a non-LR phenotype in sheep similar to those seen in bovine TSEs. However, unlike cows infected with TME (1st and 2nd passage), sheep accumulated PrPSc in the neuromuscular spindles. In conclusion, we found that sheep are susceptible to bovine passaged TME by the intracerebral route and resistant to oronasal transmission at the dosage used in this experiment. The incubation periods in affected sheep were associated with their genotype with incubation being more rapid in the VRQ haplotype.