Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus.
Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus.
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DOI：
10.1016/j.antiviral.2012.09.021
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发表时间：
2012-12
影响因子：
7.6
通讯作者：
Gershburg E
中科院分区：
文献类型：
--
作者：
Goswami R;Gershburg S;Satorius A;Gershburg E
使用一组80种蛋白激酶抑制剂分析了Ag结合B细胞受体（BCR）介导EB病毒（EBV）再活化的信号通路。广泛的蛋白激酶抑制剂Staurosporin、K252 A和PKC-412显著降低了再活化后48小时测量的EBV基因组拷贝数，这可能是由于它们的毒性更高。此外，选择的磷脂酰肌醇-3-激酶（PI 3 K）、蛋白激酶C（PKC）、促分裂原活化蛋白激酶（MAPK）和核因子κB（NF-κB）通路、糖原合成酶激酶3β（GSK-3β）、血小板衍生生长因子受体相关酪氨酸激酶（PDGFRK）、表皮生长因子受体相关酪氨酸激酶（EGFRK）也显著降低了EBV基因组拷贝数。其中，仅分别抑制MAPK途径和EGFRK的U 0126和厄布他汀类似物不抑制通过EBV早期蛋白EA-D的表达评估的病毒再活化。除了K252 A之外，没有测试的化合物影响体外EBV编码的蛋白激酶的活性。这些结果表明，BCR信号诱导的EBV再激活主要通过PI 3 K和PKC介导，而MAPK可能参与病毒复制的后期阶段。
Signaling pathways mediating Epstein-Barr virus (EBV) reactivation by Ag-bound B-cell receptor (BCR) were analyzed using a panel of 80 protein kinase inhibitors. Broad range protein kinase inhibitors Staurosporin, K252A, and PKC-412 significantly reduced the EBV genome copy numbers measured 48 hours after reactivation perhaps due to their higher toxicity. In addition, selected inhibitors of the phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways, glycogen synthase kinase 3β (GSK-3β), platelet-derived growth factor receptor-associated tyrosine kinase (PDGFRK), and epidermal growth factor receptor-associated tyrosine kinase (EGFRK) significantly reduced the EBV genome copy numbers as well. Of those, only U0126 and Erbstatin analog, which inhibit MAPK pathway and EGFRK respectively, did not inhibit viral reactivation assessed by expression of the EBV early protein, EA-D. None of the tested compounds, except for K252A, affected the activity of the EBV-encoded protein kinase in vitro. These results show that EBV reactivation induced by BCR signaling is mainly mediated through PI3K and PKC, whereas MAPK might be involved in later stages of viral replication.
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影响因子：
2.6
作者：
Bahlis, NJ;Miao, YL;Gerson, SL
通讯作者：
Gerson, SL
影响因子：
3.7
作者：
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影响因子：
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Kenney, S
影响因子：
3.7
作者：
Adamson, AL;Kenney, SC
通讯作者：
Kenney, SC