Virus and Host Interactions of the Nucleocapsid Proteins Encoded by a Plant Nucleorhabdovirus

疾病发展中的主要问题之一是病毒如何与宿主成分相互作用，以入侵细胞并绕过宿主防御。该项目将研究植物核杆状病毒家族的成员利用其宿主的蛋白质进入细胞核并建立支持病毒增殖的复合体的过程。病毒蛋白在宿主细胞核和细胞质之间的协调运输是病毒生命周期的重要组成部分。将进行生化和细胞生物学实验，以确定病毒增殖所需的三种蛋白质劫持参与蛋白质正常进出细胞核的宿主蛋白质的机制。将使用遗传和生化方法分析这三种病毒蛋白之间的相互作用，以及病毒蛋白和宿主蛋白之间的相互作用。这些实验将提供对核复制复合体形成的逐步了解。这些实验还将确定参与病毒蛋白细胞运输的宿主蛋白。弹状病毒是影响牲畜和野生动物的许多疾病的罪魁祸首，包括狂犬病和马和牛的水泡性口炎。蔬菜和大田作物的严重病害也是由弹状病毒家族的成员引起的，导致农业生产力和生态破坏的巨大损失。与弹状病毒密切相关的病毒会导致严重的人类疾病，如麻疹、腮腺炎和流感。这些病毒在疾病发展过程中有许多共同之处，可能被用于疾病控制。更好地了解病毒感染宿主的常见过程，将有助于设计干预感染过程和疾病发展的药物。该项目将向学术生涯各个层次的学生提供病毒学和分子生物学方面的培训，包括代表人数不足的少数族裔。

One of the major questions in disease development is how viruses interact with host components to invade cells and circumvent host defenses. This project will investigate the processes whereby members of the plant nucleorhabdovirus family use proteins of their hosts to enter the nucleus of cells and establish a complex that supports the multiplication of the virus. The orchestrated transport of viral proteins between the host cell nucleus and cytoplasm is an essential element of the viral life cycle. Biochemical and cell biology experiments will be carried out to determine the mechanisms by which three proteins required for virus multiplication hijack host proteins that are involved in the normal transport of proteins into and out of the nucleus. Genetic and biochemical approaches will be used to analyze interactions between the three viral proteins, as well interactions between the viral proteins and host proteins. These experiments will provide a step-by-step understanding of the formation of the nuclear replication complex. The experiments will also identify host proteins that participate in the cellular transport of the viral proteins.Rhabdoviruses are responsible for many diseases affecting livestock and wildlife, including rabies and vesicular stomatitis of horses and cattle. Serious diseases of vegetable and field crops are also caused by members of the rhabdovirus family, resulting in enormous losses to agricultural productivity and ecological damage. Viruses closely related to rhabdoviruses cause serious human diseases such as measles, mumps and influenza. These viruses have many common parallels in disease development that may be exploited for disease control. A better understanding of the common processes whereby viruses infect their hosts will be useful in designing drugs to interfere with the infection process and disease development. This project will provide training in virology and molecular biology to students at many levels of their academic careers, including underrepresented minorities.