FELINE LENTIVIRUS MODEL FOR AIDS CHEMOTHERAPY

描述：（改编自申请人的摘要） 本项目旨在开发一个用于评估 抗逆转录病毒药物，并在设计和评估中使用该系统 用于治疗人获得性免疫缺陷的治疗剂 综合征（艾滋病）。 已开发的模型是猫科动物 免疫缺陷病毒（FIV），一种与 猫的免疫缺陷与人类的艾滋病非常相似。 的 该项目的具体目标是分离和表征 FIV的叠氮胸苷（AZT）抗性突变体。 还将尝试 分离出对其他逆转录酶有抗性的FIV突变体， （RT）靶向抗病毒药物。 对这些突变体的分析将有助于 通过本实验室开发的FIV焦点感染性试验。 的 将测定每种突变体对其它抗病毒药的交叉抗性， 将进行实验以确定突变体是否恢复。 pol（指定病毒逆转录酶）基因的突变将导致 通过序列分析绘制，并将所选突变体的RT 表征了 还将尝试选择FIV的突变体， 多重耐药 选择的突变体的致病性将是 在无特定病原体的猫中进行评价。

DESCRIPTION: (Adapted from applicant's abstract) The long range goal of this project is to develop a model system for evaluation of anti-retroviral drugs and to use this system in the design and evaluation of therapeutic agents for treatment of human acquired immune deficiency syndrome (AIDS). The model which has been developed is feline immunodeficiency virus (FIV), a lentivirus associated with immunodeficiency in cats which is very similar to AIDS in humans. The specific aims of the project are to isolate and characterize sets of azidothymidine (AZT)-resistant mutants of FIV. Attempts will also be made to isolate FIV mutants resistant to other reverse transcriptase (RT)-targeted antivirals. Analysis of these mutants will be facilitated by a focal infectivity assay for FIV developed by this laboratory. The cross-resistance of each mutant to other antivirals will be determined and experiments will be carried out to determine whether the mutants revert. Mutations in the pol (specifies viral reverse transcriptase) gene will be mapped by sequence analysis and the RT of selected mutants will be characterized. Attempts will also be made to select mutants of FIV with multiple drug resistance. The pathogenicity of selected mutants will be evaluated in specific pathogen free cats.