The mechanism of Tat-enhanced reverse transcription in HIV-1

HIV-1中Tat增强逆转录的机制

• 批准号: nhmrc : 252846
• 负责人: A/Pr David Harrich
• 金额: $ 18.85万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mechanism-tat-enhanced-hiv-1/98452
• 关键词: mechanism; Tat; enhanced; reverse; transcription

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. Many HIV-1 proteins including Tat contribute to the efficiency of reverse transcription. There are two competing hypotheses to explain how Tat enhances reverse transcription. The indirect mechanism hypothesis holds that Tat-enhanced reverse transcription is due to the combined effects of the Tat-induced expression of cellular genes. The direct mechanism hypothesis is that Tat functions directly during RTN, implying it is a virion protein. Our recent genetic and biochemical data provide strong evidence that a novel form of Tat, which we call vTat, has a direct role in RTN. 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.

在逆转录过程中，正链 HIV-1 RNA 基因组被转化为双链 DNA 副本，可以永久插入宿主细胞基因组中。许多 HIV-1 蛋白（包括 Tat）有助于提高逆转录效率。有两个相互竞争的假设来解释 Tat 如何增强逆转录。间接机制假说认为，Tat 增强的逆转录是由于 Tat 诱导的细胞基因表达的综合作用所致。直接机制假设是 Tat 在 RTN 期间直接发挥作用，这意味着它是一种病毒体蛋白。我们最近的遗传和生化数据提供了强有力的证据，证明一种新形式的 Tat（我们称之为 vTat）在 RTN 中具有直接作用。本提案将研究这两个主要假设。鉴于艾滋病毒大流行的严重性以及美国最近的许多报告表明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耐药性，这些研究的结果是识别和表征了重要的新关键分子，可以针对这些分子设计抗逆转录病毒策略。