Characterization of the EBV BZLF1 Gene Product

描述（由申请人提供）：越来越多的证据表明，不仅EBV，而且其他疱疹病毒的裂解周期和细胞周期之间存在密切关系。我们最近的初步研究表明，EBV不仅在裂解性复制周期中调节细胞周期，而且再活化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，才能进入裂解复制期。本提案中概述的目标是针对研究细胞周期控制蛋白控制病毒再活化的分子机制。具体来说，我们将研究控制的立即早期启动子，Zp（BZLF 1启动子），由细胞周期调控蛋白，c-Myc，这是已知的病毒再活化过程中调制。此外，我们将评估c-Myc在调节即时早期反式激活因子Zta（BZLF 1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我们理解疱疹病毒裂解复制和细胞周期之间的密切关系。此外，他们将提供深入了解转录控制机制参与调节从潜伏期的病毒生命周期的裂解复制阶段的承诺参与的过渡。

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.