Maas Diana, Maret Claudine, Schaade Lars, Scheithauer Simone, Ritter Klaus, Kleines Michael
Division of Virology, Department of Medical Microbiology, UK Aachen, RWTH Aachen 52057, Aachen, Germany.
Med Microbiol Immunol. 2006 Dec;195(4):217-23. doi: 10.1007/s00430-006-0022-1. Epub 2006 Jun 21.
The S-adenosylhomocysteine hydrolase (SAH) and 14-3-3 zeta/phospholipase A2 (PLA2) are transcriptionally activated in parallel to the induction of the Epstein-Barr virus (EBV) lytic cycle by the ganglioside IV(3)NeuAc-nLcOse(4)Cer. For analysis of the initiation of the viral reactivation, SAH and 14-3-3 zeta/PLA2 were overexpressed. Expression of EA-D, BZLF1, and BHRF1 was increased in response to both, SAH- and 14-3-3 zeta/PLA2 overexpression indicating the initiation of the EBV lytic cycle. Expression of 14-3-3 zeta/PLA2 was shown to be increased in SAH overexpressing cells. Additionally, SAH-triggered initiation of viral reactivation could be inhibited by PLA2-specific inhibitors. The phosphorylation status of protein kinase C (PKC) was shown to be increased in SAH-overexpressing cells. PKC-specific inhibitors arrested SAH-triggered initiation of viral reactivation. Surprisingly, 14-3-3 zeta/PLA2-induced initiation of viral reactivation did not correlate with PKC activation. PKC-specific inhibitors were of no influence. SAH initiated EBV reactivation via the BZLF1-Zp and the BZLF1-Rp promoter, whereas 14-3-3 zeta/PLA2 was connected to the promoter Rp only. Our results suggest two routes of viral reactivation involving SAH, one associated with PKC and BZLF1-Zp, the other associated with 14-3-3 zeta/PLA2 and BZLF1-Rp.
神经节苷脂IV(3)NeuAc-nLcOse(4)Cer在诱导爱泼斯坦-巴尔病毒（EBV）裂解周期的同时，会转录激活S-腺苷同型半胱氨酸水解酶（SAH）和14-3-3 ζ/磷脂酶A2（PLA2）。为了分析病毒重新激活的起始过程，SAH和14-3-3 ζ/PLA2被过表达。EA-D、BZLF1和BHRF1的表达在SAH和14-3-3 ζ/PLA2过表达时均增加，这表明EBV裂解周期已起始。在SAH过表达的细胞中，14-3-3 ζ/PLA2的表达也增加。此外，PLA2特异性抑制剂可抑制SAH触发的病毒重新激活起始。在SAH过表达的细胞中，蛋白激酶C（PKC）的磷酸化状态增加。PKC特异性抑制剂可阻止SAH触发的病毒重新激活起始。令人惊讶的是，14-3-3 ζ/PLA2诱导的病毒重新激活起始与PKC激活无关，PKC特异性抑制剂对此没有影响。SAH通过BZLF1-Zp和BZLF1-Rp启动子起始EBV重新激活，而14-3-3 ζ/PLA2仅与Rp启动子相关。我们的结果表明，涉及SAH的病毒重新激活有两条途径，一条与PKC和BZLF1-Zp相关，另一条与14-3-3 ζ/PLA2和BZLF1-Rp相关。
