TAR-regulated reverse transcripition in HIV-1.

在逆转录过程中，正链HIV-1RNA基因组被转化为双链DNA拷贝，可以永久插入宿主细胞基因组。我们的实验室和其他实验室已经证明，反转录需要一系列复杂的分子，其中包括病毒RNA。这些RNA可以被组织成精细的结构，这些结构只被部分定义。遗传实验表明，这些RNA结构中的一种称为TAR，是逆转录(逆转录的第一步)的最佳启动所必需的，但确切的机制尚不清楚。我们实验室最近的进展使我们能够全面研究TAR RNA在逆转录中所起的作用。我们关于机制的主要假设是，TAR与起始复合体中的其他RNA序列或逆转录酶相互作用，以便反应是最佳的。该提案将调查这两个主要假说。鉴于艾滋病毒大流行的严重性，以及美国最近的许多报告称，大多数患者分离的病毒对至少一种抗逆转录病毒药物具有抗药性，这些研究的结果是确定和确定了可针对其设计抗逆转录病毒战略的重要新关键分子的特征。

During reverse transcription, the positive-strand HIV-1 RNA genome is converted into a double-stranded DNA copy which can be permanently insert into the host cell genome. Our laboratory and others have shown that reverse transcription requires a complex array of molecules, which includes the viral RNA. These RNA can be organised into elaborate structures that have only been partially defined. Genetic experiments have revealed that one of these RNA structures, called TAR, is required for optimal initiation of reverse transcription (the first step of reverse transcription), but the precise mechanism is unknown. Recent advances in our laboratory have enabled a comprehensive study of the role played by TAR RNA in reverse transcription. Our leading hypotheses regarding the mechanism is required that TAR interacts with other RNA sequences or Reverse transcriptase in the initiation complex so that the reaction is optimal. This proposal will investigate these two leading hypotheses. Given the enormity of the HIV pandemic and the many recent reports from the United States that most patient isolated virus is resistant to at least one antiretroviral drug, these studies have as an outcome the identification and characterisation of important new key molecules towards which antiretroviral strategies can be designed.