REPLICATIVE MECHANISMS OF THE NEGATIVE STRAND VIRUSES

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Acute viral infections are usually associated with cell killing in that major cellular functions may be inhibited or destroyed in the Process of replication of the virus. Acute viruses of the negative strand RNA group include measles, mumps, rabies, respiratory syncytial virus and the model prototype for molecular studies, vesicular stomatitis virus (VSV). The objectives of this proposal are to understand the molecular nature of virus-host interactions that lead to the cytopathology associated with infection by VSV. These experiments will focus on nucleic acid-protein interactions that are thought to affect host cell macromolecular events such as transcription and RNA processing. We will use antibody precipitation, recombinant DNA methods, cell culture techniques and in vitro biochemical analysis. Our goals are to define at the molecular level those RNA-protein contacts that alter cellular functions in order to understand mechanisms of: 1) cell killing by VSV: 2) conversion from acute to persistent infection: 3) cellular RNA transcription and processing. Thus, we are interested in VSV as a biological entity with unique properties of replication and pathology and as a probe to study the functions of mammalian cells.