To develop an understanding of the oncogenic properties of human cytomegalovirus (HCMV), we are examining molecular events involved in the control of HCMV gene expression and in the virus induction of host cell macromolecular synthesis. The proposed studies will be conducted in three phases: 1) Identification of virus genes involved in control of virus and/or cell gene expression; 2) Isolation of virus induced cell genes; and 3) Transcriptional analysis of specific virus genes. To associate function with specific virus genes, our investigations will be limited to those genes involved in either control of virus gene expression or induction of cell macromolecular synthesis. Transfection of virus DNA will be used to identify functions with specific regions on the virus chromosome. Isolation of virus induced cell genes will be accomplished by cloning cDNA copies of mRNA from virus infected cells into lambda vectors. The lambda plaques obtained will be separated for further analysis into those containing genetic information for either virus or virus induced cell genes. Transcriptional analysis will be done on immediate early and early genes for which a specific virus function has been associated and those genes which represent the most abundant classes. These specific genes will be analyzed to determine their position on the virus chromosome, direction of transcription, size, kinetics of appearance, and degree of processing. The results of these studies will enable us to associate function with a particular virus gene. In addition, we should gain insight into how a virus can modulate cellular function.
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