FIV MODEL TO STUDY DRUG THERAPIES ON LENTIVIRUS-INDUCED CNS DISEASE

迫切需要合适的动物模型来筛选有希望的动物 新的抗病毒药物，评估未来化疗靶点的适用性， 并比较不同药物和化疗方法的疗效 能够改变慢病毒诱导的中枢神经系统疾病的进程。从 该中心的初步研究和其他调查人员的工作， FIV/CAT系统已经发展成为一种合法的研究模式 慢病毒对中枢神经系统的致病作用。FIV不仅会导致疾病 这与人类艾滋病非常相似，但它在这两个方面也与艾滋病毒相似 分子和生化水平。在我们的中心，有许多参数 已经建立了监测病毒感染对中枢神经系统的影响。 我们现在想要扩大这些研究，以调查 治疗该疾病的神经学方面的药物。此外，我们 也将研究病毒耐药性这一重要的治疗问题。 一种病毒用来逃避治疗剂影响的机制。 在这个拟议的项目中，我们计划具体检查 前景看好的抗肿瘤坏死因子--NMDA受体的治疗效果 拮抗剂，新的抗病毒药物的疗效，以及 FIV所致神经系统疾病的联合治疗药物，以及 监测耐药突变株的发展并绘制基因图谱 与抗性表型相关的决定因素。我们的长期合作 目的是将FIV/CAT系统发展成为可预测的动物模型 用于评估治疗化合物对神经学的影响 慢病毒病的一些方面。重要的是不仅要研究如何 治疗剂影响疾病的神经形式，但也 病毒是如何对药物的存在做出反应的。在这一组中 在拟议的研究中，我们将研究新的治疗方法以及 抗病毒耐药突变体在慢病毒致病中的作用， 加强我们对 慢病毒、宿主和治疗剂。现在是使用这个的时候了 深入了解疾病机制并检查潜力的系统 最终可能用于人类艾滋病患者的治疗方法， 作为该中心Mitler/Darko组成部分的一部分。

There is a pressing need for appropriate animal models to screen promising new antivirals, assess the suitability of future chemotherapeutic targets, and compare different drugs and chemotherapeutic approaches in their ability to alter the course of lentivirus induced CNS disease. From the initial studies of this Center and the work of other investigators, the FIV/cat system has been developed into a legitimate model for the study of lentivirus pathogenesis of the CNS. Not only does FIV produce a disease that is very similar to human AIDS, but it is also similar to HIV at both the molecular and biochemical levels. In our Center, numerous parameters have been established to monitor the effects of virus infection on the CNS. We now want to expand these studies to investigate the effects of therapeutic agents on neurologic aspects of the disease. Additionally, we will examine the important therapeutic problem of virus resistance as well a mechanisms the virus uses to escape the effects of therapeutic agents. In this proposed project, we plan to specifically examine the effects of promising anti-TNF-alpha agents, the therapeutic outcome of NMDA receptor antagonists, the efficacy of new antiviral agents, and the effects of combined therapeutic agents on FIV induced neurological disease, as well as monitor for the development of drug-resistant mutants and map the genetic determinants associated with the resistant phenotype. Our long-term objective is to develop the FIV/cat system into a predictive animal model for assessing the effects of therapeutic compounds on the neurologic aspects of lentivirus diseases. It is important to examine not only how the therapeutic agent affects the neurologic form of the disease but also how the virus changes in response to the presence of the drug. In this set of proposed studies, we will examine new therapeutic approaches as well as the role antiviral resistant mutants play in lentivirus pathogenesis, enhancing our understanding of the interactions that occur among the lentivirus, host, and therapeutic agents. It is now time to use this system to gain insight into disease mechanisms as well as examine potential therapeutic approaches that ultimately may be used in human AIDS patients, as part of the Mitler/Darko Component of this Center.