As part of the Scripps AIDS Dementia Center Grant, we have established a feline colony for the purpose of developing the FIV/Cat system as an animal model to study the neurologic aspects of AIDS. Because of the success in developing this model, the number of investigators and experiments utilizing this system has precipitously grown since the Center's inception. Thus, the requirement for cats from both within and outside of the Center has exceeded the available funds to support the research. In this proposal, we request assistance to help further develop the FIV/Cat system as an animal model for the neurologic aspects of HIV-1 induced disease. This colony can be considered of emerging national importance. We have made great strides in developing the feline/FIV model as a legitimate system for the study of lentivirus induced neurologic disease, as several parameters have been established to monitor the effects of virus infection on the CNS. However, to fully develop the FIV/Cat system, further studies are required. Developing the FIV/Cat system as a predictive animal model to examine the effects of treatment interventions on the neurologic aspects of the disease would enhance the utility of this modeling system. To this end, we now want to expand our ongoing studies to investigate the effects of antivirals on neurologic aspects of the disease as well as the adaptive response of the virus to the drug. We propose the following specific aims: 1) specifically develop the FIV/cat system as an animal model for examining effects of antivirals on the neurologic disease progression of lentivirus infections. 2) Monitor the animals for the development of drug-resistant mutants and map the genetic determinants associated with the resistant phenotype. 3) Determine if FIV-drug resistant mutants maintain their neurovirulence. Our long term objective is to develop the FIV/cat system as a predicative animal model for assessing the effects of antiviral compounds on the neurologic aspects of lentivirus diseases. It is important to examine not only how the antivirals affect the neurologic form of the disease but also how the virus adapts to the presence of the drug. The completion of these specific aims will further validate the FIV/cat system as a predictive animal model as well as provide valuable insights into virus-host-drug interaction, thus further establishing and refining the FIV/cat systems as a research resource.
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