While oncogenic viruses are the initiator of a complex chain of events leading to malignancy, the host cell also exerts control over the expression of transformation. In the case of SV40, these controls determine, at an early stage, the type of interaction the virus will have with the infected cells: lytic or transforming. At a later stage, the host cell can still exert control over the expression of transformation by suppressing the phenotypic effect of the virus. The elucidation of the host cell factors which are important in the expression of transformation and the problem of how they interact with viral functions represent the objective of this research. We also plan to study whether integration of the SV40 genome into the DNA of transformed cells occurs at specific site(s), and whether the site of integration is important for neoplastic transformation. Among other approaches, this project will take advantage from the study of SV40 transformed cells which express the transformed phenotype in a temperature-dependent manner, and of cells which have temperature dependent serum requirements.