Latent and lytic replication of Epstein-Barr virus.

从潜伏状态诱导EB病毒裂解性复制阻断细胞周期进程并诱导ATM DNA损伤检查点信号传导。磷酸化的ATM和MRN复合物聚集在细胞核中病毒基因组合成的位点。在这里，我们报告了当诱导裂解复制时，复制蛋白A（RPA）的32 kDa亚基被广泛磷酸化。虽然RPA的总水平在整个裂解感染过程中保持不变，但DNA结合形式的水平随着裂解感染的进行而增加。磷酸化RPA被募集并保留在病毒复制区室以及磷酸化ATM中。RPA-32的磷酸化位点与EBV裂解感染时激活的ATM和DNAPK的磷酸化位点一致。由于响应于DNA损伤的RPA 32的过度磷酸化引起RPA构象的改变，其下调DNA复制的活性，但参与DNA修复过程。总的来说，EBV裂解程序可能通过RPA 32的磷酸化主动抑制染色体DNA复制，并允许过度磷酸化的RPA参与病毒复制区室中病毒DNA基因组的重组和/或修复。

Induction of Epstein-Barr virus lytic replication from latent state blocks cell cycle progression and induces ATM DNA damage checkpoint signaling. Phosphorylated ATM and MRN complex are clustered to the sites of viral genome synthesis in nuclei. Here we report that the 32 kDa subunit of replication protein A (RPA) is extensively phosphorylated when lytic replication was induced. Although the total levels of the RPA proved constant throughout the lytic infection, the levels of DNA-bound form increased as lytic infection proceeded. The phosphorylated RPA was recruited and retained in viral replication compartments as well as phosphorylated ATM. The phosphorylation sites on RPA-32 were accorded with those by ATM and DNAPK that were activated during EBV lytic infection. Since hyper-phosphorylation of RPA32 in response to DNA damage causes a change in RPA conformation that down-regulates activity in DNA replication but participates in DNA repair process. Collectively, the EBV lytic program might actively inhibit chromosomal DNA replication through phosphorylation of RPA32 and allows hyperphosphorylated RPA to be involved in recombination and/or repair of viral DNA genome in the viral replication compartments.