Influenza viruses are important human pathogens whose interactions with the infected host are complex. Since these negative strand RNA viruses possess a nuclear phase during their replication cycle, the intracellular trafficking of the viral components involves the hijacking and use of much of the host cell's transport machinery. Specifically, Aim 1 of the proposal is designed to elucidate the mechanism and the cellular transport requirements for the nuclear import of the influenza virus ribonucleoprotein (RNP). Following amplification of the incoming viral RNA in the nucleus, the newly synthesized RNA must exit into the cytoplasm.
In Aim 2 we will ask how the viral nuclear export protein (NEP) interacts with the cellular export proteins and how the viral NEP adapter interacts with the viral nucleoprotein complex. Finally, we postulate (Aim 3) that the influenza virus Ml protein has a specific budding domain which allows recruiting of the host's budding machinery, and thus drives the assembly of viral particles in the cytoplasmic membrane. Our approaches to explore the mechanisms of virus-host interactions will take advantage of our improved reverse genetics technologies to construct influenza virus mutants and of recent advances in analyzing the functions of cellular proteins.
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