X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D
X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D
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DOI：
10.1128/jvi.00154-07
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Kenney, Shannon C.
中科院分区：
文献类型：
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作者：
Bhende, Prasanna M.;Dickerson, Sarah J.;Kenney, Shannon C.
Epstein-Barr 病毒 (EBV) 在记忆 B 细胞中建立一种潜在的感染形式，而分泌抗体的浆细胞通常隐藏着裂解形式的感染。潜伏感染和裂解性 EBV 感染之间的转换是由两种病毒立即早期蛋白 BZLFI (Z) 和 BRLF1 (R) 介导的，这两种蛋白在潜伏感染的 B 细胞中不表达。在这里，我们证明了在浆细胞分化中起重要作用的细胞转录因子 X-box 结合蛋白 I (XBP-1)，也激活了两个 EBV 立即早期基因启动子的转录。在报告基因检测中，单独的 XBP-1 足以激活 R 启动子，而 XBP-1 和蛋白激酶 D (PKD) 的组合则需要有效激活 Z 启动子。最重要的是，XBP-1和激活的PKD的表达足以诱导EBV阳性鼻咽癌细胞和类淋巴母细胞中裂解性病毒基因的表达，而XBP-1小干扰RNA则抑制类淋巴母细胞中组成型裂解性EBV基因的表达。这些结果表明，浆细胞分化因子 XBP-1 与激活的 PKD 相结合，可以介导 EBV 的重新激活，从而使病毒生命周期与浆细胞分化密切相关。
Epstein-Barr virus (EBV) establishes a latent form of infection in memory B cells, while antibody-secreting plasma cells often harbor the lytic form of infection. The switch between latent and lytic EBV infection is mediated by the two viral immediate-early proteins BZLFI (Z) and BRLF1 (R), which are not expressed in latently infected B cells. Here we demonstrate that a cellular transcription factor that plays an essential role in plasma cell differentiation, X-box-binding protein I (XBP-1), also activates the transcription of the two EBV immediate-early gene promoters. In reporter gene assays, XBP-1 alone was sufficient to activate the R promoter, whereas the combination of XBP-1 and protein kinase D (PKD) was required for efficient activation of the Z promoter. Most importantly, the expression of XBP-1 and activated PKD was sufficient to induce lytic viral gene expression in EBV-positive nasopharyngeal carcinoma cells and lymphoblastoid cells, while an XBP-1 small interfering RNA inhibited constitutive lytic EBV gene expression in lymphoblastoid cells. These results suggest that the plasma cell differentiation factor XBP-1, in combination with activated PKD, can mediate the reactivation of EBV, thereby allowing the viral life cycle to be intimately linked to plasma cell differentiation.