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，我们已经建立了 用于开发FIV/Cat系统的猫科动物群体 用动物模型研究艾滋病的神经学方面。因为 开发这一模式的成功，调查人员的数量和 使用该系统的实验自 中心的诞生。因此，从内部和外部对猫的要求 中心外的资金已经超过了支持 研究。在这项提案中，我们请求援助，以进一步帮助 建立FIV/Cat系统作为神经学方面的动物模型 HIV-1引发的疾病。这个殖民地可以被认为是新兴的 对国家的重要性。我们在发展 猫科动物/FIV模型作为慢病毒研究的合法系统 诱发的神经疾病，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，要完全 FIV/Cat系统的开发，还需要进一步的研究。开发 FIV/Cat系统作为预测动物模型来检验 对这种疾病的神经学方面的治疗干预将 增强了该建模系统的实用性。为此，我们现在希望 扩大我们正在进行的研究，以调查抗病毒药物的效果 在神经学方面的疾病以及适应性反应 把病毒带到药物上。我们提出了以下具体目标：1) 专门开发FIV/CAT系统作为检测的动物模型 抗病毒药物对慢病毒神经系统疾病进展的影响 感染。2)监测动物抗药性的发展 突变株并绘制与抗性相关的遗传决定因素图 表型。3)确定FIV耐药突变株是否保持其 神经毒性。我们的长期目标是开发FIV/CAT系统 作为评估抗病毒效果的预测性动物模型 慢病毒病的神经学方面的化合物。它是 重要的是不仅要检查抗病毒药物如何影响神经系统 以及病毒如何适应这种疾病的存在 毒品。这些具体目标的完成将进一步验证 FIV/CAT系统作为预测动物模型以及提供有价值的 对病毒-宿主-药物相互作用的洞察，从而进一步建立和 将FIV/CAT系统作为研究资源进行提炼。

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.