The course of a viral infection can be quite varied (e.g. lytic, abortive, transforming, persistant or latent), each exhibiting characteristic pathogenesis. In the simplest terms the course of the infection is determined by permissivity or non-permissivity of the host cell. We propose to study the molecular mechanisms of permissivity and nonpermissivity using the simian virus 40 (SV40) system. SV40 is ideal because it is well understood and exhibits a defined infectious cycle on permissive (monkey) and nonpermissive (mouse) cells. Within the SV40 system, the control of late transcription offers an ideal parameter for these studies. Transcription of the late viral genes occurs at low levels in abortively infected mouse cells and in equally low levels early in the lytic cycle. However, in the lytic system late transcription is greatly increased at 12-18 hours postinfection allowing the full expression of the late genes. These data imply that the two types of infections may share a common initial mechanism of late transcriptional control but the progression to full expression is blocked in the nonpermissive cells. The characterization of this block addresses the mechanism of permissivity and nonpermissivity. Using the most sensitive molecular biological techniques, we propose to completely characterize SV40 late transcription in lytically and abortively infected cells, precisely defining the late transcription cycle and its dependence on other viral, or host, parameters. Differences in the cycles, comparing the two types of infections, will be determined providing data on possible permissivity mechanisms and specific areas for further study. These data will indicate factors and conditions necessary for the development of an in vitro transcription system in which late transcription and its control will be duplicated. This system will then allow us to study the factors and mechanisms involved in permissivity. Overall the project will provide a detailed study of the control of late gene expression in the lytic and abortive systems. In addition, an in vitro transcription system will be developed in which the precise mechanism of late transcriptional control can be determined. This defined system can then be used to study the block of full late expression in nonpermissive cells, thus providing an initial system for the study of permissivity.