FIV SYSTEM--A MODEL FOR LENTIVIRUS INDUCED DISEASES

作为斯克里普斯艾滋病痴呆中心拨款的一部分，我们已经建立了一个猫科动物群体，目的是开发FIV/Cat系统，作为研究艾滋病神经学方面的动物模型。由于开发该模型的成功，自中心成立以来，利用该系统的研究人员和实验人数急剧增加。因此，中心内外对猫的需求已经超过了支持研究的可用资金。在本提案中，我们请求协助进一步开发FIV/Cat系统作为HIV-1诱导疾病的神经方面的动物模型。这个殖民地为我们中心的研究人员以及几个合作研究人员提供服务。因此，我们的殖民地可以被认为具有新兴的国家重要性。我们在开发猫/FIV模型作为慢病毒诱导的神经系统疾病研究的合法系统方面取得了很大的进展，因为已经建立了几个参数来监测病毒感染对中枢神经系统的影响。然而，要充分发展FIV/Cat系统，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查治疗干预对疾病神经方面的影响将提高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，以调查抗病毒药物对疾病神经方面的影响以及病毒对药物的适应性反应。我们提出以下具体目标：1)专门开发FIV/cat系统作为动物模型，以研究抗病毒药物对慢病毒感染的神经系统疾病进展的影响。2)监测动物耐药突变体的发展，绘制与耐药表型相关的遗传决定因素。3)确定fiv耐药突变体是否保持其神经毒力。我们的长期目标是开发FIV-cat系统作为一种预测动物模型，用于评估抗病毒化合物对慢病毒疾病神经系统的影响。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，并为病毒-宿主-药物相互作用提供有价值的见解，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 serves our Center's researchers as well as several collaborating investigators. Thus, our 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 predictive animal model for assessing the effects of antiviral compounds on the neurologic aspects of lentivirus diseases. 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 interactions, thus, further establishing and refining the FIV/cat system as a research resource.