Influenza viruses pose a public health risk; effective vaccines and antivirals have alleviated the severity of disease during seasonal epidemics. However, antiviral resistance strains and novel zoonotic strains of influenza can bypass these age-old protection strategies. Understanding the viral and cellular properties required for efficient packaging of the influenza genome into progeny virions will provide novel therapeutic targets and define potential host-range restriction factors. As a post-doctoral fellow at the National Institutes of Health, I have developed two novel methods to visualize the intracellular dynamics of influenza viral RNA assembly and transport in live cells during a productive infection. These methodologies will be combined with traditional biochemical techniques to elucidate how influenza viral RNA segments are packaged by addressing the following two aims:
Aim 1 - Determine the mechanism by which all eight viral RNA segments selectively package into progeny virions and Aim 2 - Identify host components that mediate transport of influenza viral RNA from the nucleus to the plasma membrane. The proposed work will address many outstanding questions in influenza biology that are unanswered because of a lack of tools to visualize multiple viral RNA segments within a single cell and to track viral RNA movement in live cells during a productive infection. These studies will provide insight into how influenza viruses reassort in nature and identify novel host factors involved in viral RNA packaging that can be pursued as potential therapeutic targets.
Influenza viruses cause seasonal epidemics and sporadic pandemics that create a substantial public health burden with over 200,000 hospitalizations and 3,000-45,000 deaths annually. The influenza viral genome is composed of eight RNA segments, all of which must packaged into a single progeny virion for it to be infectious. The goal of this proposal is to determine how all eight segments are selectively packaged during viral infection and identify host factors involved in this process. This research will lead to novel therapeutic targets for influenza infection.
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