Vesicular stomatitis virus (VSV) will be used to study regulation of macromolecular synthesis with particular emphasis on (1) the role of interference caused by defective interfering (DI) particles in vivo and on (2) the functional interactions of the viral glycoprotein G with antibody and with the host cell. These studies will relate to the possibility of using DI particles or DI-specific nucleic acid sequences to regulate viral infections. Studies on the glycoprotein will define functional domains and elucidate the basic mechanisms by which the host defends against viral infections and how viruses overcome these defenses. These studies also provide a novel way to examine human tumor antigens. The experimental approach with DI particles will be to initiate infections in mice with known quantities of DI particles and standard VSV. The detection of synthesis of DI particles will be by Northern blotting with DI-specific cloned 32P-DNA sequences and correlating the presence of DI RNA with the disease process. Naturally virulent New Jersey isolates of VSV will be examined for their ability to generate DI particles and mapped physically against laboratory strains to determine if virulence markers are associated with certain regions of the genome. G protein will be approached via monoclonal and anti-peptide antibodies. The parameters to be measured will be neutralization, precipitation of whole virions, precipitation of G protein, and antibody-induced degradation of G protein. Mechanisms of these interactions will be elucidated. Non-VSV proteins acquired by VSV during the budding-out process from HeLA cells will be characterized in respect to their phosphate and carbohydrate content and to their synthesis and association with tumorigenesis.
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