FIV--A LENTIVIRUS MODEL FOR OPIATE EFFECTS ON DISEASE

在本提案中，我们计划应用并进一步发展FIV/CAT系统 用于研究药物滥用对慢病毒的影响 疾病进展。我们将在体外研究吗啡对 FIV复制和转录速率。 我们亦建议研究 阿片类药物对FIV感染者神经系统疾病的影响 猫有人提出，阿片剂输送给 动物可能影响研究的最终结果。 因此，我们计划 检查三种吗啡调度方法：单次注射，多次注射 急性注射和逐步增加的多次注射，导致慢性 吗啡依赖，然后通过实验强制戒断。的 这些药物方案中的每一种对FIV疾病进展的影响将是 通过一系列病毒学、免疫学和功能性CNS测定 测定。 从这项研究中获得的信息将提高我们的 了解阿片类药物作为慢病毒发病机制中的辅助因子。到 真正了解疾病的发病机制和影响因素，如 阿片类药物对过程的影响，最终必须进行研究， 动物我们已经将FIV/CAT系统发展成为一个合法的模型， 研究慢病毒对中枢神经系统的影响。由于静脉注射药物 滥用已成为获得HIV-1感染的最常见方式， 进一步了解药物滥用可能对 慢病毒疾病进展是迫切需要的。发展 FIV/cat系统转化为研究药物滥用对 慢病毒疾病进展将提供一个有价值的工具， 这种潜在的重要互动。

In this proposal, we plan to apply and further develop the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression. We will examine, in vitro, the effects of morphine on FIV replication and transcriptional rates. We also propose to examine the effects of opiates on the neurological form of the disease in FIV infected cats. It has been suggested that the manner that opiates are delivered to the animal may affect the ultimate outcome of the study. Thus, we plan to examine three morphine scheduling approaches: a single injection, multiple acute injections, and escalating multiple injections, leading to chronic morphine dependence, followed by experimentally enforced withdrawal. The effects of each of these drug schedules on FIV disease progression will be determined by a battery of virological, immunological and functional CNS assays. The information gained from this study will enhance our understanding of opiates as a co-factor in lentivirus pathogenesis. To truly understand disease pathogenesis and the effects co-factors like opiates have on the process, ultimately studies must be conducted in animals. We have developed the FIV/cat system into a legitimate model for studying the effects of lentiviruses on the CNS. Since intravenous drug abuse has become the most common mode of acquiring HIV-1 infections, a greater understanding of the potential effects that drug abuse may have on lentivirus disease progression is urgently needed. Development of the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression will provide a valuable tool to address this potentially important interaction.