Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6
Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6
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DOI：
10.4049/jimmunol.2001262
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发表时间：
2021-06-01
影响因子：
4.4
通讯作者：
Zhu, Ying
中科院分区：
文献类型：
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作者：
Cao, Wei;Guo, Yifei;Zhu, Ying
抗病毒天然免疫反应是宿主防御过程中的关键步骤，必须受到严格调控，但调控的分子机制尚不清楚。在这项研究中，我们报告了DNA和RNA病毒感染后人ATP酶Na+/K+转运亚基β 1（ATP 1B 1）的表达增加。我们发现ATP 1B 1的表达可以抑制病毒复制，并增加IFN、IFN刺激基因和炎性细胞因子的水平。通过特异性短发夹RNA敲低ATP 1B 1具有相反的效果。在病毒感染后，ATP 1B 1被诱导，与TRAF 3和TRAF 6相互作用，并增强这些蛋白的泛素化，导致下游分子磷酸化增加，包括TGF β激活的激酶1（TAK 1）和TANK结合激酶1（TBK 1）。这些结果揭示了ATP 1B 1在抗病毒先天免疫中以前未被认识到的作用，并提出了一种新的机制，在病毒感染过程中诱导IFN和促炎细胞因子。
The antiviral innate immune responses are crucial steps during host defense and must be strictly regulated, but the molecular mechanisms of control remain unclear. In this study, we report increased expression of human ATPase Na+/K+ transporting subunit beta 1(ATP1B1) after DNA and RNA virus infections. We found that the expression of ATP1B1 can inhibit viral replication and increase the levels of IFNs, IFN-stimulated genes, and inflammatory cytokines. Knockdown of ATP1B1 by specific short hairpin RNA had the opposite effects. Upon viral infection, ATP1B1 was induced, interacted with TRAF3 and TRAF6, and potentiated the ubiquitination of these proteins, leading to increased phosphorylation of downstream molecules, including TGF beta-activated kinase 1 (TAK1) and TANK-binding kinase 1 (TBK1). These results reveal a previously unrecognized role of ATP1B1 in antiviral innate immunity and suggest a novel mechanism for the induction of IFNs and proinflammatory cytokines during viral infection.