TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Virus and Prion Research
2012 Annual Report
1a. Objectives (from AD-416):
1. Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical bovine spongiform encephalopathy (BSE).
2. Investigate the horizontal transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in the absence of lambing. B. Determine routes of transmission in chronic wasting disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer.
3. Investigate determinants of CWD persistence. A. Determine CWD host range using natural routes of transmission. B. Investigate the pathobiology of CWD.
1b. Approach (from AD-416):
The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of accumulation, routes of infection, environmental persistence, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include clinical exams, histopathology, immunohistochemistry and biochemical analysis of proteins. The enhanced knowledge gained from this work will help mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.
3. Progress Report:
In research directed toward meeting objective 1 of our project plan, Investigate the pathobiology of atypical TSEs in natural hosts, we have inoculated animals for studies designed to address the pathobiology of atypical scrapie, atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of BSE. In addition, we have begun investigating the possibility that atypical scrapie was present earlier than previously detected in the national flock by analyzing archived field isolates using methods that were unavailable at the time of original diagnosis. In research pertaining to objective 2, Investigate the horizontal transmission of TSEs, we have initiated a study to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to transmit scrapie to neonatal lambs. At this time, scrapie inoculated sheep are being co-housed with pregnant ewes. For objective 3, all work planned for FY12 has been delayed until FY13 due to limited availability of animals of the required genotypes.
Greenlee, J.J., Smith, J.D., West Greenlee, M.H., Nicholson, E.M. 2012. Clinical and pathologic features of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism. PLoS ONE. 7(6):e38678.
Greenlee, J.J., Smith, J.D., Kunkle, R.A. 2011. White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation. Veterinary Research. 42(1):107.
Porcario, C., Hall, S.M., Martucci, F., Corona, C., Iulini, B., Perazzini, A.Z., Acutis, P., Hamir, A.N., Loiacono, C.M., Greenlee, J.J., Richt, J.A., Caramelli, M., Casalone, C. 2011. Evaluation of two sets of immunohistochemical and Western blot confirmatory methods in the detection of typical and atypical BSE cases. BMC Research Notes. 4:376.
Hamir, A.N. 2011. Pathology of neurologic disorders of raccoons (Procyon lotor). Journal of Veterinary Diagnostic Investigation. 23(5)873-884.
Nicholson, E.M., Greenlee, J.J., Hamir, A.N. 2011. PrPSc detection in formalin-fixed paraffin-embedded tissue by ELISA. BMC Research Notes. 4(1):432.
Greenlee, J.J., Zhang, Xia, Nicholson, E.M., Kunkle, R.A., Hamir, A.N. 2012. Prolonged incubation time in sheep with prion protein containing lysine at position 171. Journal of Veterinary Diagnostic Investigation. 24(3):554-558.
Tamguney, G., Richt, J.A., Hamir, A.N., Greenlee, J.J., Miller, M.W., Wolfe, L.L., Sirochman, T.M., Young, A.J., Glidden, D.V., Johnson, N.L., Giles, K., Dearmond, S.J., Prusiner, S.B. 2012. Salivary prions in sheep and deer. Prion. 6(1):52-61.
Sharma, V.K., Sacco, R.E., Kunkle, R.A., Bearson, S.M., Palmquist, D.E. 2012. Correlating levels of type III secretion and secreted proteins with fecal shedding of Escherichia coli O157:H7 in cattle. Infection and Immunity. 80(4):1333-1342.
Smith, J.D., Greenlee, J.J., Foster, G.H., Nicholson, E.M. 2012. Acetone precipitation of the scrapie agent results in successful recovery of PrPSc but decreased infectivity. Journal of Agricultural and Food Chemistry. 60(18):4758-4762.
Vrentas, C.E., Onstot, S., Nicholson, E.M. 2012. A comparative analysis of rapid methods for purification and refolding of recombinant bovine prion protein. Protein Expression and Purification. 82(2):380-388.
Wilson, R., Plinston, C., Hunter, N., Casalone, C., Corona, C., Tagliavini, F., Suardi, S., Ruggerone, M., Moda, F., Graziano, S., Sbriccoli, M., Cardone, F., Pocchiari, M., Ingrosso, L., Baron, T., Richt, J., Andreoletti, O., Simmons, M., Lockey, R., Manson, J.C., Barron, R.M. 2012. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. Journal of General Virology. 93(Pt 7):1624-1629.
Vrentas, C.E., Greenlee, J.J., Tatum, T.L., Nicholson, E.M. 2012. Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system. PLoS ONE. 7(8):e43060.