The overall, long-term objective of this research program is to define the roles of viral genes in controlling the outcome of infection with human adenoviruses in both permissive and non- permissive cells. We are particularly interested in trying to understand how the virus induces the selective transport of viral mRNAs which contributes to the inhibition of cellular functions in human cells, and in elucidating the roles of viral gene products in the process of oncogenic transformation of rodent cells. A variety of genetic, immunological and molecular approaches will be employed towards these ends. The following specific aims are proposed: 1) We will continue to evaluate the role of the E1B55Kd protein in regulating selective transport of mRNAs in adenovirus-infected cells, with a view to defining its mechanism of action in the process by characterizing the cellular factor(s) with which it interacts. These investigations will depend in large part upon generation of antibodies specific for the species, and upon extended genetic analysis, 2) The possible role of a viral L1 gene product in the selective transport process will be examined, by analysis of temperature-sensitive mutants which map to this region. 3) We will evaluate the role of the 55Kd protein in transformation of rodent cells by extending phenotypic analysis of a host-range mutant which is conditionally defective for the process. 4) Through analysis of a mutant which is temperature- sensitive for transformation we will evaluate the role of the C- terminal region of the E1A gene products in the transformation process. 5) By further phenotypic analysis of temperature- sensitive pol mutants we will try to define the role of the viral DNA polymerase in the transformation of rodent cells.
