Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA
Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA
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DOI：
10.1128/jvi.01339-09
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发表时间：
2010-01-15
影响因子：
5.4
通讯作者：
Suzuki, Koichi
中科院分区：
文献类型：
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作者：
Kobiyama, Kouji;Takeshita, Fumihiko;Suzuki, Koichi
形成右手螺旋结构的双链DNA （dsDNA）片段（B-DNA）刺激细胞产生I型干扰素（ifn）。虽然接头分子ifn - β启动子刺激因子1 （IPS-1）在人类细胞中介导dsdna诱导的细胞信号传导，但其潜在的分子机制尚不完全清楚。在这里，我们证明了染色体外组蛋白H2B介导人类细胞的先天抗病毒免疫反应。H2B通过一个新发现的接头CIAO （cooh末端输入蛋白9相关接头，组织组蛋白H2B和IPS-1）与IPS-1发生物理相互作用，传递dsDNA的细胞信号，但不传递免疫刺激RNA。染色体外组蛋白H2B是细胞自主反应的生物学关键，以防止DNA病毒的增殖，但不是RNA病毒。因此，本研究结果提供了证据，表明染色体外组蛋白H2B参与由dsDNA启动的信号通路，触发抗病毒先天免疫反应。
Fragments of double-stranded DNA (dsDNA) forming a right-handed helical structure (B-DNA) stimulate cells to produce type I interferons (IFNs). While an adaptor molecule, IFN-beta promoter stimulator 1 (IPS-1), mediates dsDNA-induced cellular signaling in human cells, the underlying molecular mechanism is not fully understood. Here, we demonstrate that the extrachromosomal histone H2B mediates innate antiviral immune responses in human cells. H2B physically interacts with IPS-1 through the association with a newly identified adaptor, CIAO (COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1), to transmit the cellular signaling for dsDNA but not immunostimulatory RNA. Extrachromosomal histone H2B was biologically crucial for cell-autonomous responses to protect against multiplication of DNA viruses but not an RNA virus. Thus, the present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses.