Douglas S. Lyles
My laboratory is studying the structure, assembly, and pathogenesis of enveloped RNA viruses. The goal of one research program is to define the molecular interactions involved in assembly of enveloped viruses by budding from cellular membranes. These projects are focused on vesicular stomatitis virus (VSV), a widely studied prototype enveloped virus that serves as a model for many other viruses that have envelopes as part of their structure. These studies have involved analysis of expression of wild-type and mutant forms of the viral transmembrane and internal peripheral (matrix) protein, their intracellular membrane associations, and their assembly into virions. The experimental approaches we use in this project include biophysics, genetics, and fluorescence and electron microscopy.
In a second set of projects, my laboratory is studying the molecular mechanisms involved in viral pathogenesis. The inhibition of host gene expression is a major aspect of pathogenesis for many viruses. This inhibition allows viruses to suppress the antiviral responses of their host cells. The suppression of host antiviral responses, in turn, allows viruses to spread through susceptible tissues in intact animal or human hosts. During our studies of virus assembly, our laboratory discovered that the viral matrix protein suppresses host gene expression. This activity represents a second function for matrix protein in virus-infected cells in addition to its role in virus assembly. The goal of the projects in my laboratory is to determine the mechanism by which the matrix protein inhibits host antiviral responses and how this activity of the matrix protein affects viral pathogenesis. These studies have also led to new ideas for developing viral matrix protein mutants that selectively kill cancer cells (oncolytic viruses), and viral mutants that are more effective vaccine vectors.
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