Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2004
Publication Date: 12/1/2004
Citation: Hamir, A.N., Kunkle, R.A., Richt, J.A., Cutlip, R.C., Miller, J.M., O'Rourke, K.I., Williams, E.S., Miller, M.W., Stack, M.J., Chaplin, M.J. 2004. Experimental transmission of chronic wasting disease agent to cattle by intracerebral route: final outcome of the study [abstract]. Annual Conference of the American College of Veterinary Pathologists. 41:588. Interpretive Summary:
Technical Abstract: 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 at 6 years post inoculation (PI). During that time, prion protein (PrPres) was found in the central nervous system (CNS) of 5 cattle. None of these animals had shown any specific clinical signs that were common to all. Microscopic lesions suggestive of spongiform encephalopathy in the brains of these PrPres positive animals were subtle in the first 3 and absent in the latter 2 cases. However, all 5 animals were positive for PrPres by both immunohistochemistry and Western blot. The 3 uninoculated control cattle and 8 other inoculated animals euthanized during this time did not have PrPres in their CNS. Degenerative changes indicative of neuroaxonal dystrophy (NAD) were seen in dorsal medulla oblongata and appeared to be related to advancing age in both inoculated and control cattle. Analysis of the gene encoding bovine PRNP revealed similar findings, i.e., 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 PrPres amplification occurred following direct inoculation into the brain, none of the affected animals had classical histopathological lesions of spongiform encephalopathy. Furthermore, only 38% of the inoculated cattle demonstrated amplification of PrPres. Although intracerebral inoculation is an unnatural route of exposure, and is the most severe challenge possible, this experiment shows that CWD transmission in cattle can have long incubation periods (up to 5 years). This finding suggests that oral inoculation of cattle with CWD would require not only a much larger dose of inoculum, but also, may not result in amplification of PrPres within CNS tissues during the normal lifespan of cattle. It is possible that a second bovine passage of material (brain infected with CWDmd) from this study may result in a larger proportion of affected cattle with a shortened incubation time, and may produce different clinical and pathological findings. Such a study is now in progress. Also, experimental inoculations of cattle with CWD isolates from white-tailed deer and elk are needed to compare clinicopathological findings with the present study and these studies will be initiated in the near future.