Characterization of the EBV BZLF1 Gene Produce

描述（由申请人提供）：越来越多的证据表明，不仅是eb病毒，还有其他疱疹病毒，溶解周期和细胞周期之间存在着密切的关系。我们最近的初步研究表明，EBV不仅在裂解复制周期中调节细胞周期，而且再激活受细胞周期控制途径的调节。这种形式的调控可能演变为一种策略，以确保只有当病毒检测到细胞处于最佳病毒复制的有利状态（即生长停滞）时，才会进入裂解复制阶段。在本建议中概述的目的是为了研究通过细胞周期控制蛋白控制病毒再激活的分子机制。具体来说，我们将研究细胞周期调节蛋白c-Myc对直接早期启动子Zp （BZLF1启动子）的控制，已知c-Myc在病毒再激活过程中受到调节。此外，我们将评估c-Myc在调节直接早期反激活子Zta （BZLF1的蛋白产物）的转录激活特性中所起的作用。总之，这些研究应该进一步加深我们对疱疹病毒裂解复制与细胞周期之间密切关系的理解。此外，他们将提供对转录控制机制的见解，涉及调节从潜伏期到病毒生命周期裂解复制阶段的承诺参与的转变。

DESCRIPTION (provided by applicant): There is accumulating evidence that an intimate relationship exists between the lytic cycle and the cell cycle, not only with EBV but also other herpesviruses. Our recent preliminary studies show that not only does EBV regulate the cell cycle during the lytic replication cycle but that reactivation is regulated by cell cycle control pathways. This form of regulation likely evolved as a strategy to ensure that entry into the lytic replication phase ensues only if the virus detects that the cell is in a favored status for optimal viral replication (i.e. growth arrest). The aims outlined in this proposal are directed towards investigating the molecular mechanisms through which cell cycle control proteins govern viral reactivation. Specifically, we will investigate the control of the immediate early promoter, Zp (the BZLF1 promoter), by the cell cycle regulatory protein, c-Myc, which is known to be modulated during viral reactivation. In addition, we will assess the role that c-Myc plays in regulating the transcriptional activation properties of the immediate early transactivator, Zta (the protein product of BZLF1). Together, these studies should further our understanding of the intimate relationship between lytic replication in herpesvirus and the cell cycle. In addition, they will provide insights into the transcriptional control mechanisms involved in regulating the transition from latency to committed engagement of the lytic replicative phase of the viral life cycle.