Virus Assembly, RNA Packaging, and Replication

病毒组装、RNA 包装和复制

• 批准号: 7058972
• 负责人: WEI-SHAU HU
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7058972
• 关键词: RNA; RNA binding protein; Retroviridae; capsid; murine leukemia virus; nucleic acid structure; nucleocapsid; protein structure function; virus assembly; virus replication

In addition to recombination, retroviruses also interact with one another via complementation, which involves the copackaging of viral proteins and/or RNAs. The goals of this project are to gain further insights into virus interactions by studying the mechanisms of virus assembly, RNA packaging, and replication. We have dissected a motif that is important for virus assembly and located at the C-terminal region of murine leukemia virus (MLV) capsid (CA). Mutations in this motif often cause a mutant phenotype that has virus assembly defects. These mutants produce virions that have aberrant virion morphology and package both viral RNA and ribosomal RNA. From data generated in our mutational analyses, we hypothesize that the sequences in this motif form an a-helix; maintenance of the helical structure and the phase of the helix are critical to its function. We are performing experiments to further investigate this motif to gain insight into the functional domains of CA in virus assembly. MLV and spleen necrosis virus (SNV) have a nonreciprocal relationship in RNA packaging; SNV proteins package both MLV and SNV RNA whereas MLV proteins only recognize MLV RNA. We have utilized this relationship to define the regions in the nucleocapsid (NC) domain of the Gag polyprotein and portions of the RNA in the packaging signals that are important for this specific recognition. We are further dissecting elements important in the protein-RNA interaction that define the RNA packaging specificity.

除了重组之外，逆转录病毒还通过互补作用彼此相互作用，这涉及病毒蛋白和/或RNA的共包装。该项目的目标是通过研究病毒组装，RNA包装和复制的机制来进一步了解病毒相互作用。 我们已经解剖了一个基序，这是重要的病毒组装和位于C-末端区域的小鼠白血病病毒（MLV）衣壳（CA）。该基序中的突变通常导致具有病毒组装缺陷的突变表型。这些突变体产生具有异常病毒粒子形态并包装病毒RNA和核糖体RNA的病毒粒子。从我们的突变分析中产生的数据，我们假设该基序中的序列形成a-螺旋;螺旋结构的维持和螺旋的相位对其功能至关重要。我们正在进行实验，以进一步研究这一主题，以深入了解CA在病毒组装中的功能域。 MLV和脾坏死病毒（SNV）在RNA包装中具有非互惠关系; SNV蛋白质包装MLV和SNV RNA，而MLV蛋白质仅识别MLV RNA。我们已经利用这种关系来定义的区域的核衣壳（NC）结构域的Gag多蛋白和包装信号中的RNA的部分，这是很重要的这种特异性识别。我们正在进一步剖析蛋白质-RNA相互作用中定义RNA包装特异性的重要元素。