My laboratory is studying the structure and assembly of enveloped RNA viruses. The goal of one research program is to define the molecular interactions involved in assembly 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 studies 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, such as oncogenic RNA viruses and HIV. In addition, the transmembrane interactions of the VSV envelope glycoprotein are widely studied as a model for host transmembrane proteins such as those involved in signal transduction. 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.
In a second project, Dr. Lyles is studying the mechanisms by which viruses inhibit the expression of host genes. The inhibition of host gene expression is a major aspect of cytopathology for many viruses. Thus the mechanisms involved in the inhibition are key questions in viral pathogenesis. During their studies of virus assembly, Dr. Lyles' laboratory discovered that the viral matrix protein served a second function in virus-infected cells in addition to its role in virus assembly. The VSV matrix protein inhibits host-directed transcription in the absence of any other viral gene product. The goal of this project is to determine the mechanism by which the matrix protein inhibits host transcription and identify host genes that can confer resistance to the cytopathic effects of the matrix protein. |
Recent Publications (selected):
Flood EA, Lyles DS.: Assembly of nucleocapsids with cytosolic and membrane-derived matrix proteins of vesicular stomatitis virus. Virology 261(2):295-308 (1999).
Yuan H, Yoza BK, Lyles DS.: Inhibition of host RNA polymerase II-dependent transcription by vesicular stomatitis virus results from inactivation of TFIID. Virology 251(2):383-92 (1998) .
Ahmed M, Lyles DS.: Effect of vesicular stomatitis virus matrix protein on transcription directed by host RNA polymerases I, II, and III. J Virol. 72(10):8413-9 (1998).
Lyles DS, McKenzie MO.: Reversible and irreversible steps in assembly and disassembly of vesicular stomatitis virus: equilibria and kinetics of dissociation of nucleocapsid-M protein complexes assembled in vivo. Biochemistry 37(2):439-50 (1998). |
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