The nuclear factor-kappa B (NF-κB) signaling network constitutes a first line of defense against the invading viruses. However, viruses also adopted multiple strategies to interfere with NF-κB activation. Enterovirus 71 (EV71), in the family Picornaviridae, has become the main pathogen responsible for hand, foot, and mouth disease. Recent studies have reported that the nonstructural protein 2C of EV71 inhibits TNF-α induced NF-κB activation by suppressing IKKβ phosphorylation. In our study, we found that 2C can form inclusion bodies (IBs) in infected and transfected cells. Furthermore, 2C was able to sequester IKKβ into IBs through direct interaction with IKKβ. Although 2C did not directly interact with IKKα, viral protein 2C was able to sequester the IKKα into the IBs mediated by IKKβ. Our in vitro data further demonstrated that EV71 2C could suppress IKKα phosphorylation. These all together support a novel mechanism for EV71 to escape from NF-κB response, in which the phosphorylation of IKKα was suppressed by being recruited into viral IBs in the presence of 2C and IKKβ.

中文翻译：

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肠道病毒 2C 蛋白通过将 IKKβ 和 IKKα 募集到病毒包涵体中来抑制 IKKα 磷酸化

核因子-κB (NF-κB )信号网络构成抵御入侵病毒的第一道防线。然而，病毒也采用多种策略来干扰 NF- κ B 的激活。肠道病毒 71 (EV71) 属于小核糖核酸病毒科，已成为导致手足口病的主要病原体。最近的研究报道，EV71 的非结构蛋白 2C通过抑制 IKK β磷酸化来抑制 TNF- α诱导的 NF-κB活化。在我们的研究中，我们发现 2C 可以在感染和转染的细胞中形成包涵体 (IBs)。此外，2C 能够通过与 IKK β的直接相互作用将 IKK β 隔离到 IBs中. 虽然 2C 不直接与 IKK α相互作用，但病毒蛋白 2C 能够将 IKK α隔离到由 IKK β介导的 IBs 中。我们的体外数据进一步证明 EV71 2C 可以抑制 IKK α磷酸化。这些共同支持 EV71 逃避 NF-κB 反应的新机制，其中 IKK α的磷酸化通过在 2C 和 IKK β存在下被募集到病毒 IBs 中而受到抑制。