Molecular study of reovirus outer capsid proteins: fundamental aspects and applications.

哺乳动物呼肠孤病毒在我们理解重要的生物学机制中发挥了重要作用：病毒进入，核酸和蛋白质的合成，病毒进化等等。除了作为基础研究工具的兴趣之外，还设想了呼肠孤病毒的可能应用。有些病毒，如呼肠孤病毒，现在可以成为我们的“盟友”，而不仅仅是敌人。呼肠孤病毒感染人类和大范围动物物种的能力表明了为这些病毒开发新应用的可能性。此外，现在清楚地确定呼肠孤病毒优先感染和杀死癌细胞;因此它们是开发“病毒疗法”抗癌治疗的有吸引力的候选者。我的实验室在过去的18年里一直积极参与呼肠孤病毒生物学各个方面的研究。分子生物学、生物化学和经典遗传学方法对于剖析病毒蛋白的结构和功能特别有用。现在建议继续进行这些研究，以更好地了解病毒复制周期的基本知识，这对这些病毒的实际应用开发至关重要。三种不同的蛋白质将被研究：这些蛋白质涉及病毒进入，正常细胞和癌细胞之间的区分，以及病毒组装。我们将利用病毒基因序列和突变体的可用性来确定各种蛋白质的作用，并使用基因工程工具进一步修改它们。我们相信，这些研究应该大大有助于我们的长期目标，旨在开发和优化呼肠孤病毒在动物和人类生物学中的实际应用。

Mammalian reoviruses have played an important role in our understanding of important biological mechanisms: virus entry, synthesis of nucleic acids and proteins, virus evolution, and many more. In addition to their interest as fundamental research tools, possible applications for reoviruses are envisaged. Some viruses, such as reoviruses, can now become our "allies" rather than just enemies to fight. The ability of reoviruses to infect humans and a large range of animal species suggests the possibility of developing novel applications for these viruses. Furthermore, it is now clearly established that reoviruses preferentially infect and kill cancer cells; they are thus attractive candidates for the development of "virotherapy" anticancer treatments. My laboratory has been actively involved in the study of various aspects of the biology of reoviruses, and this for the last 18 years. Molecular biology, biochemistry, and classical genetics approaches, have been especially useful to dissect the structure and function of viral proteins. It is now proposed to pursue these studies to develop a better fundamental understanding of the viral replication cycle, an understanding that is essential for the development of practical applications for these viruses. Three different proteins will be studied: these are involved in virus entry, discrimination between normal and cancer cells, and virus assembly. We will take advantage of the availability of viral gene sequences and mutants to determine the role of the various proteins and to further modify them using genetic engineering tools. We believe that these studies should significantly contribute to our long-term objectives aimed at developing and optimizing practical applications for reoviruses in animal and human biology.