The Epstein-Barr virus LF2 protein inhibits viral replication
The Epstein-Barr virus LF2 protein inhibits viral replication
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DOI：
10.1128/jvi.00315-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Johannsen, Eric
中科院分区：
文献类型：
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作者：
Calderwood, Michael A.;Holthaus, Amy M.;Johannsen, Eric
EB病毒（EBV）潜伏感染到裂解性复制的转变由两种转录调节因子Zta和Rta控制。我们先前报道了由LF 2基因编码的EBV蛋白与Rta结合，并且可以在报告基因测定中抑制Rta活性。我们现在报告，LF 2协会与Rta的背景下，EBV感染的细胞诱导裂解复制。LF 2对Rta的抑制作用发生在上皮细胞和B细胞中，并且这种下调是启动子特异性的：LF 2使BALF 2、BMLF 1和BMRF 1启动子的Rta活化降低60 - 90%，但不显著降低其自身启动子（Rp）的Rta活化。LF 2通过至少两种机制降低Rta活化：降低DNA结合和通过Rta酸性活化结构域干扰转录活化。LF 2的共表达还特异性地诱导小泛素样修饰物SUMO 2和SUMO 3对Rta的修饰。我们进一步证明LF 2过表达阻断了由Rta或Zta诱导的EBV感染细胞的裂解活化。我们的研究结果表明，LF 2，从EBV参考株B 95 -8中删除的基因，编码一种有效的EBV复制抑制剂，他们建议，未来的EBV复制研究需要考虑LF 2对Rta活性的潜在影响。
The switch from Epstein-Barr virus (EBV) latent infection to lytic replication is governed by two transcriptional regulators, Zta and Rta. We previously reported that the EBV protein encoded by the LF2 gene binds to Rta and can inhibit Rta activity in reporter gene assays. We now report that LF2 associates with Rta in the context of EBV-infected cells induced for lytic replication. LF2 inhibition of Rta occurs in both epithelial and B cells, and this downregulation is promoter specific: LF2 decreases Rta activation of the BALF2, BMLF1, and BMRF1 promoters by 60 to 90% but does not significantly decrease Rta activation of its own promoter (Rp). LF2 decreases Rta activation by at least two mechanisms: decreased DNA binding and interference with transcriptional activation by the Rta acidic activation domain. Coexpression of LF2 also specifically induces modification of Rta by the small ubiquitin-like modifiers SUMO2 and SUMO3. We further demonstrate that LF2 overexpression blocks lytic activation in EBV-infected cells induced with Rta or Zta. Our results demonstrate that LF2, a gene deleted from the EBV reference strain B95-8, encodes a potent inhibitor of EBV replication, and they suggest that future studies of EBV replication need to account for the potential effects of LF2 on Rta activity.