The Cellular Actin Network and Virus Replication

University Of Kentucky Research Foundation, Lexington KY

Investigators

Abstract

This project will dissect how plant viruses interact with the actin cytoskeleton, one of the intracellular protein scaffolds along which much molecular movement (trafficking) occurs. Viruses appear to target the actin network to reprogram cellular pathways so that they support the virus life cycle instead of performing normal cellular functions. It has been observed that viruses modify the functionality of the actin network, thereby dramatically reorganizing the infected cells to support viral replication. A potential societal benefit of this research is a deeper understanding of virus-host interactions that could lead to potent new anti-viral approaches. In addition, this work will provide training for graduate students and a postdoctoral fellow and will provide opportunities for high school students to participate in supervised research and present their results at high school science competitions. The project will exploit the new discovery that plant viruses target cellular cofilin, a major regulator of the actin network. The research will address the questions: How does a virus exploit cofilin to interfere with the actin network? How does actin organization control viral replication in cells? The project will take advantage of yeast as a model host for viruses, allowing the testing of well-characterized cofilin and actin mutants in virus replication. In vitro assays with purified components and microscopy-based analysis of the actin network in yeast and plant cells accumulating viruses will be used to unravel the steps in the viral replication process that are affected by actin. Proteomic analysis of the viral replication complex will determine which of the host proteins that are subverted by viruses are regulated by the actin network.