The purpose of the proposed research is to investigate the nature of virus-induced cell fusion. This process will be studied with mutants of Herpes Simplex Virus(HSV) which cause cells to fuse during a productive viral infection. Wild type HSV does not produce cell fusion, but mutants can be isolated that do. Our approach in determining the molecular basis of viral induced cell fusion will be to genetically separate the cell fusion process from other events in the cell, and then to biochemically determine which membrane molecules are involved in the process. For the genetic separation, a large number of HSV mutants causing cell fusion will be isolated and characterized by complementation and recombination tests. Biochemical studies will be used to compare the synthesis of new membrane molecules in mutant and wild type viral infections, and to compare their incorporation into cell plasma membranes and mature virions. Comparisons will also be made on the cell plasma membranes to detect modifications or loss of pre-existing membrane molecules. Proteins and glycoproteins will be separated by SDS gel electrophoresis, lipids will be separated by thin layer chromatography, and fatty acids will be separated by gas-liquid chromatography.