TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research Unit
Title: Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy
Submitted to: World Association of Veterinary Laboratory Diagnosticians
Publication Type: Proceedings
Publication Acceptance Date: August 10, 2007
Publication Date: November 11, 2007
Citation: Hamir, A.N., Cutlip, R.C., Miller, J.M., Kunkle, R.A., Richt, J.A., Greenlee, J.J., Nicholson, E.M., Kehrli, Jr., M.E. 2007. Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy. In: Proceedings of the World Association of Veterinary Laboratory Diagnosticians 13th International Symposium, November 11-14, 2007, Melbourne, Australia. p. 29.
Introduction: Experimental cross-species transmission of TSE agents provides valuable information for identification of potential host ranges of known TSEs. This report provides a synopsis of TSE (scrapie, CWD, TME) transmission studies that have been conducted in cattle and compares these findings to those seen in animals with BSE.
Materials & Methods: Generally 6-month-old bull calves were obtained and assigned to inoculated and control groups. Inoculated calves were housed in a Biosafety Level 2 isolation barn at the National Animal Disease Center (NADC), Ames, Iowa. Calves were inoculated intracerebrally with 1 ml of a 10% TSE brain inoculum.
Results: Results of various TSE cattle experiments with intracerebral inoculation of scrapie, CWD and TME are shown in tabular form (Table 1).
Table 1. Comparison of experimental scrapie, chronic wasting disease (CWD) and transmissible mink encephalopathy (TME) in cattle inoculated by the intracerebral route during first passage of the inocula.
Abnormal CNS signs:
Scrapie. Anorexia, weight loss, leg and back stiffness. Some showed incoordination and posterior weakness. Eventual severe lethargy.
CWD. Anorexia, weight loss, occasional aimless circling, listlessness and excited by loud noises.
TME. Variable hyperexcitability with occasional falling to the ground. Some showing circling and aggressive behavior.
Incubation (survival) time: Scrapie. 14 – 18 months. CWD. 23 – 63 months. TME. 13 – 16 months.
Attack rate: Scrapie. 100%. CWD. CWD from mule deer: 38%. CWD from elk: 86%. TME. 100%
Scrapie. Some vacuolation and central of chromatolysis of neurons.
CWD. Isolated vacuolated neurons, a few degenerate axons, and a mild astrocytosis.
TME. Extensive vacuolation of neuronal perikarya and neuropil. Presence of mild multifocal gliosis.
Western blot (brainstem):
Scrapie. All three isoforms of PrP**res present. CWD. All three isoforms of PrP**res seen. TME. All three isoforms of PrP**res seen.
PrP**res in lymphoreticular tissues: Scrapie. Not present. CWD. Not present. TME. Not present.
PrP**res in CNS:
Scrapie. Present within perikaryon and processes of neurons.
CWD. Multifocal distribution with labeling primarily in glial cells (astrocytes).
TME. Diffusely present and usually evenly distributed in neuropil.
1. All three TSEs agents (scrapie, CWD and TME) are capable of propagating in cattle tissues when administered intracerebrally.
2. All three TSEs can be distinguished from each other and from BSE when inoculated intracerebrally by histopathology, immunohistochemistry and Western blot techniques.