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机制方面发挥了重要作用：病毒进入、核酸和蛋白质的合成、病毒进化等。除了它们作为基础研究工具的兴趣外，还设想了呼肠孤病毒的可能应用。一些病毒，如呼肠孤病毒，现在可以成为我们的“盟友”，而不仅仅是敌人来战斗。呼肠孤病毒能够感染人类和多种动物物种，这表明有可能为这些病毒开发新的应用。此外，现在已经清楚地证实，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。在过去的18年里，我的实验室一直积极参与呼肠孤病毒生物学的各个方面的研究。分子生物学、生物化学和经典遗传学方法对剖析病毒蛋白质的结构和功能特别有用。现在建议进行这些研究，以更好地从根本上了解病毒的复制周期，这一理解对于开发这些病毒的实际应用至关重要。将研究三种不同的蛋白质：它们与病毒进入、正常细胞和癌细胞之间的区分以及病毒组装有关。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，这些研究应该对我们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的长期目标做出重大贡献。

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.