The molecular biology of vesicular stomatitis virus will be studied in relation to the control of gene expression and the interference caused by defective interfering (DI) particles. Both in vitro and in vivo virus-specific RNA will be analyzed in detail, especially in relation to fine structure and sequence of the oligonucleotides. Heteroduplex RNA molecules made by annealing mRNA to virion RNA will be utilized for the physical isolation of specific cistrons on the virion RNA and for the mapping of ts mutants. These ts mutants will also be analyzed phenotypically by analyses of their proteins and RNA's. In particular, the functional roles of NS, L and N proteins during the synthesis of RNA will be studied in detail. DI particle RNA will be similarly analyzed and mapped relative to RNA from standard virus. The interference caused by DI particles will be studied in relation to age susceptibility in young and old mice. Primary cultures will allow biochemical characterization of the differences in susceptibility.