The theme of this program project grant is the molecular biology and genetics of viral carcinogenesis and the relationship of the processes involved in viral carcinogenesis and replication to normal cellular processes. Temin, Risser, and Panganiban study avian and murine retroviruses (spleen necrosis virus (SNV) and murine leukemia virus (MLV)); Risser also studies human immunodeficiency virus (HIV); Mertz studies simian virus 40 (SV40), a monkey papova virus; and Sugden studies Epstein-Barr virus (EBV), a human herpes virus. Temin plans studies that will enhance the ability to construct retroviruses with different properties and will use this ability to study retrovirus replication, variation, and evolution and the genetic mechanisms of oncogenesis. Mertz's objective is to understand at the molecular level the mechanisms by which the expression of the late genes of SV40 are regulated and the ways in which the virus-encoded large T antigen affects that regulation. Panganiban's research will examine the post-transcriptional expression and post-translational regulation of the retroviral pol gene open reading frame and the activity of one of its products, the int protein, as well as examining the function of the retrovirus env gene product. Risser will study the role of envelope protein expression in the retrovirus life cycle and pathogenesis. His research group will determine the role of regions of the envelope gene in virus function, identify and characterize the viral and cellular determinants of viral host range and cytopathology, and determine the pathologic consequences of high level viral env gene expression in cells and organisms. Sugden's research centers on the identification and characterization of those genetic elements of Epstein-Barr virus (EBV) required for efficient immortalization of human B-lymphocytes and for latent infection of human epithelial cells.