Construction And Application Of PSUPER Retro RNAi System Of The Specific Silencing EBV Early Gene BHRF1

The Epstein Barr virus (EBV) is a ubiquitous human herpesvirus that establishes a persistent infection and is carried by greater than 90% of the world's population. In immunocompetent individuals, EBV contributes to a number of human cancers including the endemic form of Burkitt's lymphoma(BL), nasopharyngeal carcinoma (NPC), Hodgkin's disease, and a small percentage of gastric carcinomas and T cell lymphomas. It is well-known that in the EBV-associated tumor tissues, EBV only exists in malignant cells, but not in normal cells. Further more, in the EBV-positive cancer tissues, EBV genome has been detected in almost all malignant cells. These finding suggest that EBV may be the ideal target to cure the EBV-positive tumor. So we can take measure to kill EBV-positive tumor cells specifically based on the difference between EBV-positive tumor cells and normal cells. EBV usually infects the cells latently and different EBV-associated tumor tissues appear different form of latent, in turn, the expression of the oncogene is not same as well. The EBV latent membrane protein (LMP1) gene and nucleoantigen gene EBNA2 are virus-oncogene, which can induce malignant transformation of cells. EBNA2 is the earliest expressed virus encoding protein in the process of EB virus transformed B lymphocyte. It could activate cell cycle by enhancing transcription of the cell cyclin D2 and strengen inducing expression of LMP1 to anti-apoptosis protein bcl-2. The high level of LMP1 expression may inhibit differentiation of human epithelial cells, induce tumor formation of human epithelial cells and rat cells in athymic mouse vivo, block P⁵³ mediated apoptosis by activating A20, and induce cell canceration which has important function in B lymphocytic transformation in vitro. However, the expression of LMP1 could not be detected in a few EBV-positive tumors.The Epstein - Barr virus (EBV) BHRF1 protein is coded in the EBV BamHI fragment H rightward open reading frame 1 and shows partial sequence and functional homology to anti-apoptotic Bcl-2. Several reports have shown that the BHRF1 protein...