The human cytomegaloviruses (HCMV), members of the herpesvirus group, are capable of producing latent and persistent infections and are associated with numerous diseases including Kaposi's sarcoma. These multiple pathogenic effects are likely the result of a complex interplay of viral gene products and induced and repressed cellular gene functions. We have been studying the organization and expression of selected regions of the HCMV genome strain AD169 and the association of HCMV with Kaposi's sarcoma. In this grant application, our proposed studies focus on the regulation of transcription and the function of the protein products encoded by the following early RNA transcripts: 1) the 2.7 kb and 1.2 kb RNA transcripts encoded by the repeat bounding the long unique segment of the genome; and 2) the 2.2 kb RNA transcripts containing the cell-related and the complement of the v-myc-related sequences (encoded by EcoRI fragments d-R). To begin to elucidate the role of cellular factors in HCMV pathogenesis, we also propose to identify and characterize specific cellular genes activated during the permissive infection, with emphasis on the early times post infection. In addition, we propose to continue our analysis of Kaposi's sarcoma specimens from patients with AIDS for HCMV gene transcription, cellular oncogene transcription, and HTLVIII/LAV genetic information. For the above studies, we will use molecular biological techniques including recombinant DNA technology, nucleic acid hybridization with highly defined reagents, immunoprecipitation with specific antibodies, in vitro translation, DNA sequencing, DNA transfection, construction and use of retrovirus vectors expressing antisense RNA transcripts, and in situ cytohybridization. The long range goals of this research are to define at the molecular level the expression of the HCMV genome and to elucidate mechanisms of HCMV pathogenesis, including the role of HCMV in oncogenesis.
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