Vincent R. Racaniello
Department of Microbiology
701 W. 168th St. Room 1310B
New York, NY 10032
Voice: 212-305-5106 or- 1468
1984 Searle Scholar
Research in this laboratory is aimed at understanding the replication and pathogenesis of poliovirus, the RNA-containing virus that causes poliomyelitis. Our studies focus on the interaction of virus with its cell receptor, PVR, the cell function of PVR, and the molecular basis of poliovirus pathogenesis.
Poliovirus infection begins when the virus binds to a cell surface receptor and subsequently releases the viral nucleic acid into the cell. Poliovirus is a particularly good model for studying these interactions. The three dimensional structure of poliovirus has been determined by X-ray crystallography, the cell receptor for poliovirus has been identified, and genetic manipulation of the virus is possible with infectious cDNA copies of the viral genome. One goal of our research is to use these experimental tools to identify regions of the capsid and PVR that initially interact and lead to the structural transitions associated with uncoating of the viral RNA. These questions are addressed by the construction and analysis of mutants of the viral capsid and the cellular receptor.
To learn more about how poliovirus causes disease, we have established a new mouse model for poliomyelitis. Mice are normally resistant to poliovirus infection, but transgenic mice expressing PVR develop poliomyelitis after inoculation with virulent strains of the virus. This mouse model is being used to address questions on the pathogenesis of poliomyelitis, such as how poliovirus infection is restricted to specific cell types such as neurons, how the virus spreads in the infected animal, and the basis for the attenuation phenotype of the live poliovirus vaccines.To identify the specific cell function of PVR, extracellular and intracellular ligands of the protein are being sought. In addition, insertional mutagenesis of a murine PVR homologue is in progress. The phenotype of mice lacking this gene may provide information on the function of the receptor in cells.
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