Protein synthesis control by vesicular stomatits virus

描述（由申请方提供）：感染宿主细胞后，水泡性口炎病毒（VSV）在宿主蛋白质合成被破坏的同时翻译其必需蛋白质。该建议旨在了解VSV mRNA使用宿主细胞翻译机制翻译的分子机制，同时宿主mRNA翻译被阻断。第一个目的是确定VSV mRNA翻译是否通过顺式作用序列促进，或者来自病毒基因组的转录是否允许这些mRNA被翻译。第二个目标建立在我最初研究的数据基础上，这些数据表明VSV感染以类似于细胞应激反应的方式改变了翻译装置。这个目标将扩大我的发现，即VSV能够在压力下在细胞中复制，并将评估VSV杀死缺氧癌细胞的能力，并作为靶向缺氧区域的抗癌疗法。在这第二个目标中，我将进一步检验VSV感染后的翻译和细胞应激后的翻译相似的假设。这些目标一起形成一个建议，研究VSV成功地利用主机翻译装置的机制。这些项目旨在开发一个独立的研究计划，重点是发现更多关于病毒和宿主蛋白质翻译机制的信息，并有兴趣将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.