The goal of this work is to add to the evidence and ultimately to help prove that Epstein-Barr virus is the cause of malignant transformation and that this effect is accomplished by continuing and restricted expression of specific gene functions. The association of EBV with one benign and two malignant conditions provides a unique opportunity to determine at the cellular level and in molecular terms how one virus can have such a wide spectrum of clinical expression. The transformation of lymphocytes and malignant conversion of epithelial cells may be the result of stringent regulation of viral functions. Elucidation of the biochemical events related to transformation or malignancy is dependent upon the analysis of the patterns of viral gene expression and the parameters governing that expression for each clinical phenotype. The availability of cloned EBV DNA sequences makes it possible to map accurately regions of transcription with limited amounts of RNA. This proposal will provide the primary data on EBV transcription in NPC. In order to maintain latency of successful infection within an organism, herpesviruses must maintain very tightly regulated expression. It is possible that different EBV functions would be required for limited expression within epithelial cells or in any cell in vivo, where the cells are under organismal control and subjected to hormonal effects or immunological surveillance.
The specific aims of this research proposal are to: 1) determine which viral sequences are transcribed within the epithelial cells in NPC tissue. The regions of DNA homologous to both polyadenylated and nonpolyadenylated RNAs will be determined. 2) compare the regions of transcription of a human tumor specimen before and after cultivation in nude mice. 3) utilizing RNA purified from the nude mouse grown tumors, determine the size and direction of the EBV transcripts to compare to the transcripts detected in in vitro grown cell lines and identify any novel mRNAs. 4) determine if acyclovir has any effect on the synthesis of particular transcripts in NPC tumors grown in nude mice treated with acyclovir.
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