The cytomegaloviruses (CMV) are ubiquitous species-specific agents which are capable of producing persistent and latent infections and are associated with numerous diseases including Kaposi's sarcoma. A great deal of evidence suggests that these viruses can interact with leukocytes. The major objective of our research is to utilize murine cytomegalovirus (MCMV) infections in mice as an animal model system for uniting the studies on the molecular biology and in vivo pathology of the virus. In particular, we propose to characterize the molecular events involved in the acute infection of mice by MCMV, in the establishment of latency, and in the reactivation of latent virus. In these studies, we will analyze primarily the interaction of MCMV with leukocytes especially in the spleen. Our plan of approach is 1) to identify the cell types involved during the acute and latent infections, 2) to characterize the viral gene products expressed during the acute infection, 3) to determine whether all viral gene products are expressed at a low level during latency or whether there is a specific block in viral replication, and 4) to analyze the patterns of viral DNA replication and RNA transcription following reactivation of latent virus. We also propose to block in vivo MCMV infection with the use of a retrovirus vector directing the synthesis of antisense RNA from the major MCMV immediate early gene. For these studies, we will use molecular biological techniques including recombinant DNA technology, nucleic acid hybridization with highly defined reagents, DNA sequencing, in situ cytohybridization, and immunocytochemistry. The long range goals are to provide the essential foundation for defining the molecular events involved in CMV pathogenesis in humans and for developing an approach for interception of the virus.
