ANTIVIRAL EFFECTS ON FIV NEUROLOGIC DISEASE PROGRESSION

作为斯克里普斯艾滋病痴呆症中心赠款的一部分，我们建立了 一个猫科动物群，目的是开发FIV/Cat系统， 动物模型来研究艾滋病的神经方面。 因为 成功开发这一模式，调查人员的数量和 自2000年以来，利用该系统的实验急剧增长， 中心的成立。 因此，对猫的要求从内部和 该中心以外的资金已超过支持该中心的可用资金 research. 在这一建议中，我们请求援助， 开发FIV/Cat系统作为神经学方面的动物模型 HIV-1引起的疾病。 这个殖民地可以被认为是 国家重要性。 我们在发展 猫/FIV模型作为研究慢病毒的合法系统 诱发的神经系统疾病，因为已经确定了几个参数 监测病毒感染对中枢神经系统的影响。 然而，为了充分 开发FIV/Cat系统，需要进一步研究。 发展 FIV/Cat系统作为预测动物模型，以检查 对该疾病的神经方面的治疗干预将 增强了该建模系统的实用性。 为此，我们现在要 扩大我们正在进行的研究， 对疾病的神经学方面以及适应性反应， 病毒与药物之间的联系 我们提出以下具体目标：1） 专门开发FIV/猫系统作为动物模型， 抗病毒药物对慢病毒神经系统疾病进展的影响 感染. 2)监测动物是否出现耐药性 突变体，并绘制与抗性相关的遗传决定因素 表型。 3)确定FIV耐药突变体是否保持其 神经毒性 我们的长期目标是开发FIV/CAT系统 作为评估抗病毒药物作用的预测性动物模型 这些化合物对慢病毒疾病的神经学方面的影响。 是 重要的是不仅要检查抗病毒药物如何影响神经系统， 疾病的形式，以及病毒如何适应病毒的存在。 药 这些具体目标的实现将进一步证实 FIV/cat系统作为预测动物模型以及提供有价值的 深入了解病毒-宿主-药物相互作用，从而进一步建立和 完善FIV/CAT系统作为研究资源。

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.