ERK- and JNK-Dependent signaling pathways contribute to Bombyx mori nucleopolyhedrovirus infection
ERK- and JNK-Dependent signaling pathways contribute to Bombyx mori nucleopolyhedrovirus infection
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DOI：
10.1128/jvi.01683-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Shimada, Toru
中科院分区：
文献类型：
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作者：
Katsuma, Susumu;Mita, Kazuei;Shimada, Toru
丝裂原活化蛋白激酶（MAPK）在病毒感染中起重要作用。为了探讨杆状病毒感染诱导的细胞内信号转导途径，我们研究了MAPK在家蚕核型多角体病毒（BmNPV）感染BmN细胞中的作用。我们发现，细胞外信号调节激酶（ERK）激酶和c-Jun氨基末端激酶（JNK）的特异性抑制剂显着减少闭塞体（OB）的形成和出芽病毒（BV）的生产。接下来，我们在感染后不同时间（p.i.）应用抑制剂后定量OB和BV的产生。当在感染后12小时施用时，抑制剂在不同程度上显著降低OB和BV的产生，表明这些抑制剂降低BmNPV的感染性发生在感染的后期。此外，我们观察到，这些抑制剂显着抑制或失调延迟早期，晚期和非常晚的基因产物的表达。磷酸化MAPK特异性抗体的Western blot分析表明ERK和JNK在BmNPV感染后期被激活。此外，MAPK激活的幅度和模式依赖于感染的多重性。为了验证抑制剂对BmNPV感染的影响，我们还尝试敲除B。mori基因BmErk和BmJnk，分别编码ERK和JNK。BmERK和BmJNK的敲低导致OB和BV的产生减少，证实BmERK和BmJNK参与BmNPV感染过程。综上所述，这些结果表明，MAPK信号通路的激活是BmNPV有效感染所必需的。
Mitogen-activated protein kinases (MAPKs) often play important roles in virus infection. To explore intracellular signaling pathways induced by baculovirus infection, we examined the involvement of MAPKs in Bombyx mori nucleopolyhedrovirus (BmNPV) infection of BmN cells. We found that specific inhibitors of extracellular signal-regulated kinase (ERK) kinase and c-Jun NH2-terminal kinase (JNK) significantly reduced occlusion body (OB) formation and budded virus (BV) production. Next, we quantified OB and BV production after applying the inhibitors at different times postinfection (p.i.). The inhibitors significantly reduced OB and BV production to various extents when applied at 12 h p.i., indicating that the reduction of BmNPV infectivity by these inhibitors occurs at the late stage of infection. Also, we observed that these inhibitors markedly repressed or deregulated the expression of delayed early, late, and very late gene products. Western blot analysis using phospho-MAPK-specific antibodies showed that ERK and JNK were activated at the late stage of BmNPV infection. In addition, the magnitude and pattern of MAPK activation were dependent on the multiplicity of infection. To verify the effects of the inhibitors on BmNPV infection, we also attempted to knock down the B. mori genes BmErk and BmJnk, which encode ERK and JNK, respectively. Knockdown of BmErk and BmJnk resulted in the reduced production of OBs and BVs, confirming that BmERK and BmJNK are involved in the BmNPV infection process. Taken together, these results indicate that the activation of MAPK signaling pathways is required for efficient infection by BmNPV.