2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38523EBNA 1 is one of Epstein-Barr virus (EBV) latent genes, which is only expressed in type I latency of Burkitt’s lymphoma (BL) cells. This implicates that EBNA 1may play an important role in the type I latency cells. EBNA 1 transcript in the type I latency cells is specifically initiated from Q promoter (Qp). Therefore, the investigation of regulation of Qp by cellular factors will be the best way to explore why EBV maintains latent infection in the type I cells. In preliminary studies, we have identified a transcription factor, human immunodeficiency virus-enhancer binding protein 2 (HIV-EP2), which was associated with the upstream region of Qp, through the yeast one-hybrid system. Besides that, we performed EMSA assay system to also demonstrate the association of HIV-EP2 with the region of Qp in vitro. To further understand what HIV-EP2 plays a role in cells, we tried to observe the distribution of HIV-EP2 expression in human tissues by using northern blotting. The result indicated that the expression of HIV-EP2 mainly occurs in lymphatic and brain organs. This observation showed us that the HIV-EP2 could be a key factor involved in the growth control of lymphatic and neuron cells. In the meantime, we discovered that HIV-EP2 inhibited not only the transcription of EBV latent protein, EBNA1 but also that of Zta protiein, an EBV immediate early gene product, which switched latent infection to lytic cycle. Obviously, these preliminary results implicate the expression of HIV-EP2 will possibly lead to the change of EBV life cycle. In order to answer to riddle, we first intend to realize the contribution of HIV-EP2 protein to EBV and associated cellular gene expression in the infected cells in this project. Secondly, we continue to trace the role of HIV-EP2 in the EBV infected cells and clarify the relationship of HIV-EP2 with other cellular proteins. Furthermore, we hope to explore how HIV-EP2 cooperates with cellular proteins and EBV genes in the infected cells. Once accomplished, the basic concept of the EBV gene regulation by cellular factors in the infected cells will allow us to improve the control strategies of EBV-induced diseases. These control strategies will be a striking criterion for preventing from emergent diseases caused by EBV in the future.EB病毒感染細胞後其基因表現甚為複雜，其中EBNA 1是唯一會在第一型潛伏性巴 克氏淋巴瘤[Burkitt，s lymphoma (BL)]中表現的基因。並且此基因只會藉由Q啟動子來啟 動轉錄反應。暗示著EBNA 1蛋白質對於維持第一型潛伏細胞可能扮演重要角色。因此 在第一型潛伏細胞中，針對EBNA 1蛋白質研究基因調控機制，將可更深入了解其角色。 經由前人研究結果顯示，在BL細胞中有某些蛋白質會與Q啟動子相互結合。這些與其結 合的蛋白質很可能會影響EBNA 1啟動子的調控，但目前尚未有足夠證據證實。在我們 初步研究結果得知，利用酵母菌one-hybrid的方法可以找到一個能與Q啟動子區域結合 的轉錄因子，這個轉錄因子稱為human immunodeficiency virus-enhancer binding protein 2 (HIV-EP2)。由於目前對於HIV-EP2是否會影響Q啟動子活性的情況並不清楚，為了能夠 暸解HIV-EP2與Q啟動子之間的關係，我們使用electrophoretic mobility shift assay(EMSA) 的方法去證實。結果再次証明HIV-EP2在哺乳動物細胞內也會與Q啟動子區域結合。除 此之外，為了更瞭解HIV-EP2在細胞内的角色，我們偵測HIV-EP2在人體組織中的分布 情形。結果發現其主要表現在淋巴系統及神經相關器官。此表示HIV-EP2可能與淋巴與 神經細胞生長調控有關。同時，我們又發現HIV-EP2不僅抑制EBNA1蛋白質表現也抑制 Zta蛋白質表現。這意味著它可能影響到EB病毒生活史。為了解開這個謎，我們在這個 計劃中，首先深入探討HIV-EP2對於EB病毒及與其相關細胞基因表現的貢獻。其次，我 們希望繼續釐清HIV-EP2與其他相關細胞基因間的關係並闡述其間如何合作來調控EB 病毒基因。一旦完成，將可提供病毒學家對細胞基因如何調控EB病毒的新概念。而此新 概念的建立，在未來確實有助於防治EB病毒所引起的疾病。Project