Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route

• Published in: Journal of veterinary diagnostic investigation 2005-05, Vol.17 (3), p.276-281
• Main Authors: Hamir, A.N, Kunkle, R.A, Cutlip, R.C, Miller, J.M, O'Rourke, K.I, Williams, E.S, Miller, M.W, Stack, M.J, Chaplin, M.J, Richt, J.A
• Format: Article
• Language: English
• Subjects: animal diseases; Animals; Cattle; cattle diseases; Cattle Diseases - pathology; Cattle Diseases - transmission; cerebrum; chronic wasting disease; Deer; deer diseases; disease transmission; histopathology; incubation period; inoculation methods; Medulla Oblongata - pathology; Odocoileus hemionus; prions; Wasting Disease, Chronic - pathology; Wasting Disease, Chronic - transmission
• ISSN: 1040-6387; 1943-4936
• DOI: 10.1177/104063870501700313

This communication reports final observations on experimental transmission of chronic wasting disease (CWD) from mule deer to cattle by the intracerebral route. Thirteen calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Three other calves were kept as uninoculated controls. The experiment was terminated 6 years after inoculation. During that time, abnormal prion protein (PrP(res)) was demonstrated in the central nervous system (CNS) of 5 cattle by both immunohistochemistry and Western blot. However, microscopic lesions suggestive of spongiform encephalopathy (SE) in the brains of these PrP(res)-positive animals were subtle in 3 cases and absent in 2 cases. Analysis of the gene encoding bovine PRNP revealed homozygosity for alleles encoding 6 octapeptide repeats, serine (S) at codon 46, and S at codon 146 in all samples. Findings of this study show that although PrP(res) amplification occurred after direct inoculation into the brain, none of the affected animals had classic histopathologic lesions of SE. Furthermore, only 38% of the inoculated cattle demonstrated amplification of PrP(res). Although intracerebral inoculation is an unnatural route of exposure, this experiment shows that CWD transmission in cattle could have long incubation periods (up to 5 years). This finding suggests that oral exposure of cattle to CWD agent, a more natural potential route of exposure, would require not only a much larger dose of inoculum but also may not result in amplification of PrP(res) within CNS tissues during the normal lifespan of cattle.