FELINE LENTIVIRUS MODEL FOR AIDS CHEMOTHERAPY

描述：(改编自申请者摘要)远景目标 本项目的目的是开发一个评估模型系统 并将该系统应用于抗逆转录病毒药物的设计和评价 治疗人类获得性免疫缺陷的治疗药物 综合症(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。这个 该项目的具体目标是分离和表征几组 抗叠氮胸苷(AZT)FIV突变体。我们还将尝试 分离对其他逆转录酶具有抗性的FIV突变体 (RT)-靶向抗病毒药物。对这些突变体的分析将是便利的 通过本实验室建立的FIV局灶性传染性试验。这个 将确定每个突变体对其他抗病毒药物的交叉耐药性 将进行实验以确定突变体是否会回复。 Poll(特定病毒逆转录酶)基因的突变将是 通过序列分析和所选突变体的RT将被映射 特色化的。还将尝试选择FIV的突变体 多重耐药。选定的突变体的致病性将是 在无特定病原体的猫身上进行评估。

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.