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

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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.