Detailed Biography:

Morphogenesis of a DNA tumor virus. Recent studies appear to associate natural SV40 strains with human brain tumors of early childhood. The goal of our research is to understand the pathways that contribute to the formation of a DNA tumor virus, namely, SV40, and to understand how tumor antigens play a role in viral morphogenesis. Our work concerns defining the individual protein domains of SV40 structural proteins that determine the individual steps in the morphogenesis and relating these domains to their biological activities. We are using various molecular biological, genetic, biochemical,cell biological and immunological approaches to ask various questions, specifically: (1) What is the structural determinant for the nuclear targeting of an infectious virion particle, and what is the mechanism of the targeting? (2) What components of viral proteins are important for viral DNA targeting? (3) How infecting virions move tiwards the nucleus in the cytoplasm? (4) How do viral structural proteins fold into correct, functional structures? (5) How are individual viral proteins intracellularly targeted to the nucleus following their synthesis? (6) What are the determinants of individual viral proteins that specify protein-protein interactions? (7) Where and how do the interactions of each viral protein leading to virion assembly occur? (8) What are the determinants that initiate genome packaging and how does the packaging occur? A basic understanding of the functional determinants is indispensable toward understanding which ones mediate infection and which ones prevent the spread of the DNA tumor viruses. For example, successful identification of the specific viral components or viral protein domains that mediate effective nuclear targeting of SV40 DNA may lead to the development of a general, effective means to exogenously introduce DNA or tumor killing agent into mammalian cells.