Canine distemper virus (CDV), a morbillivirus closely related to human measles virus (MV) is a viral pathogen of dogs. Infection in dogs may result in the development of several different disease syndromes including: acute fatal encephalitis, chronic lymphoplasmacytic encephalitis with demyelination and persistent progressive encephalomyelitis. The latter reproduces many of the features of human MV-related encephalitis including subacute sclerosing panencephalitis (SSPE) and possibly multiple sclerosis. Thus, the overall objective of this research is to use CDV infection in gnotobiotic dogs to elucidate mechanism(s) of neurotropic paramyxovirus disease in the natural host system. Other factors being equal, development of any of the above forms of central nervous system (CNS)-interreaction is dependent upon the quantity and quality of virus entering the neuropil. Experiments are designed to investigate mechanisms of viral entry into the CNS at the capillary endothelial cell interface. We wish to determine the relative importance of leukocyte-associated, plasma phase and platelet-associated virus in initiating endothelial-CNS infection. Further, we wish to test our hypothesis that the major form of infective virus produced in vivo by infected macrophages consists chiefly of substructural ribonucleoprotein complexes. We wish to determine more precisely the mechanism(s) of CDV-associated immunodysregulation, especially upn lymphokine production as a major extraneural complicating effect of CDV infection. Finally, we wish to examine collected CNS tissues for the mode of viral expression coincident wth CNS lesions by delineation of virion polypeptide synthesis by immunolabeling techniques and to correlate these findings with retained viral genetic information as determined by in situ hybridization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS014821-16A1
Application #
3395771
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-05-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
16
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Axthelm, M K; Krakowka, S (1987) Canine distemper virus-induced thrombocytopenia. Am J Vet Res 48:1269-75
Axthelm, M K; Krakowka, S; Gorham, J R (1987) Canine distemper virus: in vivo virulence of in vitro-passaged persistent virus strains. Am J Vet Res 48:227-34
Axthelm, M K; Krakowka, S (1987) Canine distemper virus: the early blood-brain barrier lesion. Acta Neuropathol 75:27-33
Axthelm, M K; Krakowka, S (1986) Immunocytochemical methods for demonstrating canine distemper virus antigen in aldehyde-fixed paraffin-embedded tissue. J Virol Methods 13:215-29