GAG PROTEIN/RNA INTERACTIONS IN THE HIV LIFECYCLE

描述：研究人员建议描述HIV-1 Gag/y的特征 体外分子细节的相互作用，并评价其在 HIV-1感染生物学。高分辨率足迹和诱变 将被执行以绘制所需的y中的特定残基和结构 GAG结合、RNA二聚及其他体外活性。核糖核酸 将研究GAG结合引起的构象变化，以及 调查人员将确定与个别网站的绑定如何促进或 调整y函数。Y基因存在明确缺陷的HIV-1前病毒突变株 将被创建并测试它们对病毒感染性的影响，RNA 包装保真度、颗粒形态和反转效率 抄写。最后，调查员将测试新识别的 与HIV-1 Gag有比y更强亲和力的异源RNA配体 因为它们有能力取代HIV-1RNA中的天然y基因座，并作为 Y功能和病毒复制的竞争性反式抑制物。

DESCRIPTION: The investigator proposes to characterize the HIV-1 Gag/y interaction in molecular detail in vitro, and to evaluate its role in the biology of HIV-1 infection. High-resolution footprinting and mutagenesis will be performed to map specific residues and structures in y required for binding of Gag, RNA dimerization, and other in vitro activities. RNA conformational changes induced by Gag binding will be investigated, and the investigator will determine how binding to individual sites promotes or regulates y functions. Mutant HIV-1 proviruses with defined defects in y will be created and tested for their effects on virus infectivity, RNA packaging fidelity, particle morphology, and the efficiency of reverse transcription. Finally, the investigator will test newly-identified heterologous RNA ligands that bind with greater affinity than y to HIV-1 Gag for their ability to replace the native y locus in HIV-1 RNA and to act as competitive trans-inhibitors of y function and virus replication.