STRUCTURAL INVESTIGATION OF THE HANTAAN VIRUS L PROTEIN

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DESCRIPTION (adapted from applicant's abstract): Bunyaviruses represent the largest family of negative stranded RNA viruses. Each contains a genome consisting of three RNA segments wrapped in a nucleoprotein complex. Most Bunyaviruses are propagated in an insect vector with the notable exception of Hantaviruses which are carried in rodents. Hantaan virus, the initial Hantavirus, was first shown to be the causative agent of Korean Hemorraghic Fever, a disease endemic in the Orient. Viruses closely related to Hantaan virus, however, have a worldwide distribution and to be associated with hemorraghic fever. With the recent unexpected outbreak of acute pulmonary syndrome in the Southwest, also caused by a hantavirus referred to as Sin Nombre Virus (SNV), the identification of additional cases in other regions of the country, and the characterization of several new species of hantavirus in North America, it is important to obtain a detailed understanding of the hantavirus life cycle. The long-term goals of the application are to elucidate the mechanisms of hantavirus mRNA synthesis and RNA replication. In this proposal, the applicant will focus on developing a topological map of the viral L protein. Due to the anticipated difficulty in obtaining large amounts of pure L protein sufficient for structural studies, we propose a novel approach to generating, identifying and characterizing active subdomains of the L protein. The results of the proposed studies will serve as the groundwork for future studies on viral transcription and replication.