The objective of this proposal is to understand the mechanism by which cells tune-down the synthesis of macromolecules under conditions of stress and after infection by cytotoxic viruses. After exposure of cells to hypertonic medium and infection by vesicular stomatitis virus (VSV), several phosphorylated components and a protein associate with ribosomes. Experiments using temperature sensitive mutants of VSV indicate that the appearance of these components correlates with protein and ribosomal RNA synthesis inhibition. The identification of the components and their role in protein synthesis inhibition are being investigated. Studies using temperature sensitive mutants of VSV also suggest a role of virion L protein and newly synthesized N (and possibly NS) proteins in cell killing and protein synthesis inhibition. Their role in these processes is also being studied.