Either ZEB1 or ZEB2/SIP1 Can Play a Central Role in Regulating the Epstein-Barr Virus Latent-Lytic Switch in a Cell-Type-Specific Manner
Either ZEB1 or ZEB2/SIP1 Can Play a Central Role in Regulating the Epstein-Barr Virus Latent-Lytic Switch in a Cell-Type-Specific Manner
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DOI：
10.1128/jvi.02706-09
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Mertz, Janet E.
中科院分区：
文献类型：
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作者：
Ellis, Amy L.;Wang, Zhenxun;Mertz, Janet E.
我们以前报道，细胞蛋白ZEB 1可以抑制EB病毒（EBV）BZLF 1基因的表达，在瞬时转染试验中直接结合其启动子，Zp。我们还报道，EBV含有一个2-bp的取代突变的ZEB-结合ZV元件的Zp自发地重新激活出潜伏期裂解复制的频率比野生型EBV。在这里，使用小干扰RNA（siRNA）和短发夹RNA（shRNA）技术，我们明确表明，ZEB 1确实是维持EBV潜伏期在一些上皮细胞和B淋巴细胞系的关键球员。然而，在其他EBV阳性上皮细胞和B细胞系中，另一种锌指E-box结合蛋白ZEB 2/SIP 1是关键参与者。ZEB 1和ZEB 2都可以通过ZV元件结合Zp。在仅含有ZEB 1的EBV阳性细胞中，ZEB 1的敲低导致潜伏期外的病毒再活化，并合成EBV立即早期和早期裂解基因产物。然而，在含有两种ZEB的EBV阳性细胞中，ZEB 2而不是ZEB 1是与Zp结合的主要ZEB家族成员。ZEB 2而非ZEB 1的敲低导致EBV裂解性再激活。因此，我们得出结论，无论是ZEB 1或ZEB 2可以发挥核心作用，在维持EBV潜伏期，这样做的细胞类型依赖性的方式。
We previously reported that the cellular protein ZEB1 can repress expression of the Epstein-Barr virus (EBV) BZLF1 gene in transient transfection assays by directly binding its promoter, Zp. We also reported that EBV containing a 2-bp substitution mutation in the ZEB-binding ZV element of Zp spontaneously reactivated out of latency into lytic replication at a higher frequency than did wild-type EBV. Here, using small interfering RNA (siRNA) and short hairpin RNA (shRNA) technologies, we definitively show that ZEB1 is, indeed, a key player in maintaining EBV latency in some epithelial and B-lymphocytic cell lines. However, in other EBV-positive epithelial and B-cell lines, another zinc finger E-box-binding protein, ZEB2/SIP1, is the key player. Both ZEB1 and ZEB2 can bind Zp via the ZV element. In EBV-positive cells containing only ZEB1, knockdown of ZEB1 led to viral reactivation out of latency, with synthesis of EBV immediate-early and early lytic gene products. However, in EBV-positive cells containing both ZEBs, ZEB2, not ZEB1, was the primary ZEB family member bound to Zp. Knockdown of ZEB2, but not ZEB1, led to EBV lytic reactivation. Thus, we conclude that either ZEB1 or ZEB2 can play a central role in the maintenance of EBV latency, doing so in a cell-type-dependent manner.