Understanding the Pseudodiploidy of the Retroviral Genome

了解逆转录病毒基因组的伪二倍体

• 批准号: 7965709
• 负责人: WEI-SHAU HU
• 金额: $ 41.3万
• 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/7965709
• 关键词: Affect; Biological; Biological Assay; Cell fusion; Dimerization; Elements; Event; Family; Gagging; Genome; Goals; HIV Drug Resistance Program; Infection; Length; Light; Play; Process; Proviruses; RNA; Regulator Genes; Reporting; Retroviridae; Role; Site Visit; System; Virion; Virus; cis acting element; dimer; gag Gene Products; monomer; research study

Retroviridae are unique among virus families in that one virion packages two full-length copies of its genome. However, each infectious event generates only one provirus; thus, retroviruses are pseudodiploid. We do not fully understand the benefit of pseudodiploidy, and we propose to examine the benefit of packaging two RNAs in one virion. Additionally, the exact mechanisms that retroviruses use to package two RNAs are not currently understood. We have performed experiments examining the mechanisms of copackaged RNA partner selection and have demonstrated that the DIS sequence plays an important role in this process. In our experimental system, we can increase or decrease heterozygous virus formation by manipulating the DIS sequences of the two viruses. These results suggest that Gag recognizes and packages an RNA dimer rather than two monomers. We will continue to dissect elements important to packaging the RNA dimer, including cis-acting elements such as DIS and trans-acting elements such as Gag proteins. Using a cell-fusion assay, we will elucidate when and where selection of copackaged RNA partners occur. These studies will shed light on one of the most fundamental features of retroviral replication and will illustrate both the advantages and the limitations of pseudodiploidy. [Corresponds to Hu Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]

逆转录病毒科在病毒家族中是独特的，因为一个病毒体包装两个 基因组的全长拷贝。然而，每个感染事件仅产生一个前病毒; 因此逆转录病毒是假二倍体。我们并不完全理解 假二倍体，我们建议检查包装两个RNA在一个病毒粒子的好处。 此外，逆转录病毒包装两种RNA的确切机制目前还不清楚。 明白我们已经进行了实验，研究共包装RNA伴侣的机制， 选择，并已证明DIS序列在这一过程中起着重要作用。 在我们的实验系统中，我们可以增加或减少杂合病毒的形成， 操纵这两种病毒的DIS序列。这些结果表明，加格认识到， 并且包装RNA二聚体而不是两个单体。我们将继续分析 重要的是包装RNA二聚体，包括顺式作用元件，如DIS和 反式作用元件如Gag蛋白。使用细胞融合试验，我们将阐明 以及共包装RNA伴侣的选择发生的位置。这些研究将阐明 逆转录病毒复制的最基本特征，并将说明这两个 假二倍体的优点和局限性。[对应于4月份的Hu项目2 2007年艾滋病耐药项目现场访问报告]