The goal of this proposal is to understand the regulation of EBV gene expression in immortalized B cells.
Two specific aims concern regulation of two promoters, Wp and Cp, that allow expression of the six EBNA genes, while a third aim concerns alternative splicing of the Wp- and Cp-initiated transcripts. The proposed studies also extend to a murine herpesvirus, gamma HV68.
Four specific aims are: (1) To investigate initiation of EBNA gene transcription upon infection of peripheral B cells by determining whether multiple W promoters are active during early stages of infection, whether the first one or two W promoters are required for establishment of latency, to map and characterize the cis and trans elements that are required for initial Wp activity. (2) To study regulation of EBNA gene expression in low-passage EBV-immortalized cells by characterizing LCL's that have been immortalized with viruses containing mutations in cis elements that are suspected to be involved in regulating C and W promoters; by characterizing Cp regulation in newly established LCLs that exhibit significant Wp activity; and by assessing the role of the Notch signaling pathway in maintenance of B-cell immortalization. (3) To investigate processing of long primary EBNA gene transcripts in EBV immortalized B cells. (4) To identify the cis- and trans-acting elements which are required for maintenance of latently infecting genomes of gamma herpesvirus 68.
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