Project 2

药物滥用是感染HIV-1的一个重要途径。甲基苯丙胺和慢病毒感染都会引起神经毒性和免疫抑制。然而，HIV-1和甲基苯丙胺在神经系统疾病进展中的相互作用仍不清楚。缺乏信息的部分原因是，鉴于吸毒人口众多，收集人的数据特别困难。此外，侵入性调查措施不可能在人身上进行。因此，迫切需要适当的动物模型来检查甲基苯丙胺对慢病毒疾病进展的作用，特别是CNS形式的疾病。我们现在已经开发了猫/FIV模型作为研究lf慢病毒诱导的神经系统疾病的合法系统。我们现在已经开发了猫/FIV模型作为研究慢病毒诱导的神经系统疾病的合法系统。FIV不仅产生与人类艾滋病非常相似的疾病，而且在分子和生物化学水平上也与HIV相似。已经建立了许多参数来监测病毒注射对CNS的影响。我们现在想应用这个模型来了解甲基苯丙胺可能与这种慢病毒诱导的疾病的神经形式之间的潜在相互作用。在这个计划中。我们计划通过比较单次注射、多次急性注射和长期给药甲基苯丙胺的效果，来检查甲基苯丙胺对FIV复制和转录效率的体外作用，以及研究甲基苯丙胺给药方案对FIV疾病进展的结果。为了更好地了解药物滥用对慢病毒疾病进展的影响，至关重要的是要有一个相关的模型系统，但经得起彻底的测试和评估。FIV/cat系统作为研究天然慢病毒感染的最小模型，为评价甲基苯丙胺对慢病毒诱导的疾病的影响提供了最经济和有用的系统。该提案的长期目标是将FIV/cat系统充分开发为预测性动物模型，用于评估非法药物使用对这种慢病毒诱导疾病的神经形式的影响。

Drug abuse is an important route of exposure for HIV-1. Both methamphetamine and lentiviral infections cause neurotoxicity and immunosuppression. However, the interactions between HIV-1 and methamphetamine in neurologic disease progression remain unclear. Part of the reason for this lack of information is that gathering data in people is particularly difficult, given the populations that engage in drug abuse. Additionally, invasive investigative measures are not possible in people. Thus, there is a pressing need for appropriate animal models to examine the role of methamphetamine on lentivirus disease progression, particularly the CNS form of the disease. We have now developed the feline/FIV model as a legitimate system for the study lf lentivirus induced neurologic disease. We have now developed the feline/FIV model as a legitimate system for the study of lentivirus induced neurologic disease. 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. Numerous parameters have been established to monitor the effects ov irus injection on the CNS. We now want to apply this model to understand the potential interactions that methamphetamine may have with the neurological form of this lentivirus induced disease. In this proposed project. we plan to examine the in vitro effects of methamphetamine on the replication and transcriptional efficiency of FIV as well as investigate the outcome of methamphetamine schedule on FIV disease progression, by comparing the effects of administering methamphetamine in a single injection, multiple acute injections, and chronic administration. In order to better understand the effects of drug abuse on lentiviral disease progression, it is critical to have a model system that is pertinent, yet amenable to thorough testing and evaluation. As the smallest model for the study of natural lentivirus infections, the FIV/cat system provides the most economical and useful system for evaluating the effects of methamphetamine on lentivirus induced disease. The long-term objective of this proposal is to fully develop the FIV/cat system into a predictive animal model for assessing the effects of illicit drug use on the neurological form of this lentivirus induced disease.