Phase I research will involve participation in a currently-funded five-year project titled Feline Neurotropic Retroviruses (NIH, NINDS, NS28510) which has the overall goal of developing an animal model of the neurologic abnormalities associated with the human immunodeficiency virus (HIV) infection. Neurotropic feline retroviruses are being isolated and molecularly cloned to be characterized viral genetically, in vitro, and ultimately inoculated into specific pathogen free cats. Neuropathology will be the focus of this Special Emphasis Research Career Award (SERCA) concentrating on the following Specific Aims: 1)Characterization of retrovirus-associated morphologic lesions within the nervous system in both naturally-occurring and experimentally-infected cats, 2)Correlation of clinical neurological deficits with the characterized morphologic lesions within the nervous system of retrovirus-infected cats, 3)Identification of the target cells within the nervous system of retrovirus-infected cats, and 4)Correlation of in situ cytokine production with the characterized morphologic lesions within the nervous system of retrovirus-infected cats. Phase I studies will involve the following techniques, light, electron, and confocal microscopy, immunohistochemistry and in situ hybridization, morphometry and tomography. It is anticipated that Phase II research will utilize the acquired expertise and results obtained from Specific Aims 1 and 2 to focus and extend investigations relating to Specific Aims 3 and 4 above.
| Mitchell, T W; Buckmaster, P S; Hoover, E A et al. (1999) Neuron loss and axon reorganization in the dentate gyrus of cats infected with the feline immunodeficiency virus. J Comp Neurol 411:563-77 |
| Mitchell, T W; Buckmaster, P S; Hoover, E A et al. (1998) Axonal sprouting in hippocampus of cats infected with feline immunodeficiency virus (FIV). J Acquir Immune Defic Syndr Hum Retrovirol 17:1-8 |
| Mitchell, T W; Rojko, J L; Hartke, J R et al. (1997) FeLV envelope protein (gp70) variable region 5 causes alterations in calcium homeostasis and toxicity of neurons. J Acquir Immune Defic Syndr Hum Retrovirol 14:307-20 |
