Protein synthesis control by vesicular stomatits virus

描述(申请人提供)：水疱性口炎病毒(VSV)感染宿主细胞后，在翻译其必需蛋白质的同时，宿主蛋白质合成被破坏。这一建议旨在了解VSV mRNA通过宿主细胞翻译机制进行翻译的分子机制，同时阻止宿主mRNA的翻译。第一个目的是确定VSV mRNA的翻译是否通过顺式作用序列来促进，或者是否来自病毒基因组的转录允许这些mRNAs被翻译。第二个目的建立在我最初研究的数据基础上，这些数据表明VSV感染以一种类似于细胞应激反应的方式改变了翻译装置。这一目标将扩大我的发现，即VSV能够在压力下的细胞中复制，并将评估VSV杀死缺氧癌细胞的能力，并作为针对缺氧区域的抗癌治疗。在第二个目标中，我将进一步检验VSV感染后的翻译与细胞应激后的翻译相似的假设。这些目的共同构成了一项研究VSV成功利用宿主翻译设备的机制的建议。这些项目旨在开发一个独立的研究计划，专注于发现更多关于病毒和宿主蛋白翻译的机制，并有兴趣将所学到的经验应用于癌症治疗。

DESCRIPTION (provided by applicant): Following infection of host cells, vesicular stomatitis virus (VSV) translates its essential proteins at the same time that host protein synthesis is disrupted. This proposal is directed at understanding the molecular mechanisms by which VSV mRNA is translated using the host-cell translation machinery at the same time that host mRNA translation is blocked. The first aim is to determine whether VSV mRNA translation is facilitated through cis acting sequences, or whether transcription from the viral genome allows these mRNAs to be translated. The second aim builds on data which arose from my initial studies here which indicated that VSV infection alters the translation apparatus in a manner that is similar to the cell-stress response. This aim will expand on my finding that VSV is capable of replicating in cells under stress and will assess VSV's ability to kill hypoxic cancer cells and serve as an anticancer therapy targeting regions of hypoxia. In this second aim I will further test the hypothesis that translation following VSV infection and translation following cell stress are similar. Together these aims form a proposal that studies the mechanisms by which VSV successfully utilizes the host translation apparatus. These project is designed to develop an independent research program focused on discovering more about mechanisms of both viral and host protein translation with an interest in applying the lessons learned to cancer therapy.