The Immunologic Control of Gene Expression

The main focus of our laboratory has been in the area of immunologic control of gene expression. Two systems are being examined: (1) immunoregulation of natural products of monocytes, macrophages, and hepatocytes and (2) immunologic control of viral gene expression. In the first area, we have used individual complement components as the target molecules and have elucidated a system in which a network of antibody and lymphoid cells can suppress the synthesis and secretion of the complement molecules. This control has been shown to be chiefly posttranscriptional, and we are currently determining the relative importance of nuclear processing, transport to the cytoplasm, and translation of the mRNA of the suppressed protein. The second area of research is an outgrowth of the first. It examines the hypothesis that similar specific immunologic networks regulate the synthesis of individual viral proteins within infected cells to control viral replication without lysing the cells. Measles-infected murine macrophage cell lines constitute the experimental system currently in use for these studies, since measles virus causes a persistent, non-lytic infection in these cells; the virus itself is relatively simple (encoding only 6 proteins); and the use of cell lines derived from inbred mice enables a variety of cellular studies without encountering problems of histoincompatibility.