The proposed research programs are designed to gain insight at the molecular level of control processes which regulate gene expression, virus replication and cell growth - primarily in mammalian cell-virus systems, and with an emphasis on mechanisms of transcription and translation. Specific areas of research include: optimization of in vitro systems for high fidelity translation of viral and cellular mRNAs; coupling of viral transcription-translation processes in vitro; resolution of interferon action studied in an in vitro transcription-translation system; mechanism of L-histidinol inhibition of protein synthesis and its differential effect on cellular and viral mRNA translation; de-acylation as a control mechanism in translation; mechanism of viral control of cellular protein synthesis; role of initiation factors in translation of cellular and viral mRNA; regulation of mRNA translation by translational control RNA (tcRNA); cleavage of viral polyproteins in vivo and in vitro; induction of RNase by dsRNA and viruses; induction of interferon by (plus or minus) stranded defective interfering particles; effect of interferon on modulation of viral transcription; cell killing by viruses and by double-stranded RNA; RNase-inhibitors as regulators of cell growth and function; induction of deoxythymidylate synthetase by polyoma virus; use of nanomelic mutants in differentiation of chondrocytes; growth regulation of chondrocytes by proteochondroitin sulfate; role of cell surface proteoglycans in differentiation; cell-free synthesis of tubulin I and II; control of redundancy of rRNA cistrons; BUDR and redundancy of rRNA DNA; mechanisms regulating nucleolar transcription; action of RNA polymerase II as an autorepressor; antimutator genes; selection of ts-mutants in RNA synthesis. Kinetics of synthesis of paramyxovirus proteins; biogenesis of viral membranes. BIBLIOGRAPHIC REFERENCES: Cell killing by viruses IV. Cell killing and protein synthesis inhibition by vesicular stomatitis virus require the same gene functions. J.L. Marvaldi, J. Lucas-Lenard, M.J. Sekellick and P.I. Marcus, Virology, In press, 1977. Defective interfering particles with covalently linked RNA induce interferon. P.I. Marcus and M.J. Sekellick, Nature, In press, 1977.