GAG PROTEIN/RNA INTERACTIONS IN THE HIV LIFECYCLE

描述：研究者建议表征HIV-1 Gag/y 体外分子细节的相互作用，并评估其在 HIV-1感染生物学。 高分辨率足迹和诱变 将进行映射所需的y中的特定残基和结构 Gag结合、RNA二聚化和其他体外活性。 RNA 将研究由Gag结合诱导的构象变化，并且 研究者将确定与单个研究中心的结合如何促进或 调节y功能。 在y中具有确定缺陷的突变型HIV-1前病毒 将被创建并测试它们对病毒感染性、RNA 包装保真度，颗粒形态，以及反转效率 转录。 最后，研究人员将测试新发现的 与HIV-1 Gag结合亲和力大于γ的异源RNA配体 因为它们能够取代HIV-1 RNA中的天然y位点， γ功能和病毒复制的竞争性反式抑制剂。

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.