Lack of essential role of NF-κB p50, RelA, and cRel subunits in virus-induced type 1 IFN expression
Lack of essential role of NF-κB p50, RelA, and cRel subunits in virus-induced type 1 IFN expression
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DOI：
10.4049/jimmunol.178.11.6770
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Beg, Amer A.
中科院分区：
文献类型：
--
作者：
Wang, Xingyu;Hussain, Sofia;Beg, Amer A.
1型干扰素（ifn - α - β）在宿主抗病毒反应和ter诱导的信号传导中发挥关键作用。IFN调节因子（IRF）和nf - κ B转录因子被认为是病毒诱导的IFN- β mRNA表达的关键。尽管最近的研究已经证明了IRF3和111177的重要作用，nf - κ B因子在ifn - β（或IFN-a）表达中的确切作用仍然未知。利用缺乏NF-kappa B家族不同成员的小鼠，我们研究了NF-kappa B在仙台病毒和新城疫病毒感染中调节1型IFN表达的功能。令人惊讶的是，病毒感染p50(-/-), RelA/p65(-/-), cRel(-/-), p50(-/-) cRel（-/-）和p50(-/-)RelA（-/-）小鼠的小鼠胚胎成纤维细胞（mef）后，ifn - β和ifn - α的表达被强烈诱导。与野生型mef相比，只有RelA（-/-）和p50(-/-) RelA(-/-) mef表现出ifn - β表达的适度降低。为了克服不同NF-kappa B亚基之间的功能冗余，我们在p50(-/-)RelA(-/-) mef中表达了显性负I kappa Ba蛋白，以抑制剩余NF-kappa B亚基的激活。虽然病毒感染这些细胞不能诱导可检测到的nf - κ B活性，但仙台病毒和新城疫病毒感染均导致ifn - β的强烈表达。病毒感染树突状细胞或tlr9配体CpG-D19处理来自RelA（-/-）或p50(-/-)cRel（-/-）小鼠的浆细胞样树突状细胞也诱导了I型IFN的强劲表达。因此，我们的研究结果表明，NF-KB亚基p50、RelA和cRel在病毒诱导的1型IFN表达中起相对较小的作用。
Type 1 IFNs (IFN-alpha beta) play pivotal roles in the host antiviral response and in TER-induced signaling. IFN regulatory factor (IRF) and NF-kappa B transcription factors are thought to be crucial for virus-induced mRNA expression of IFN-beta. Although recent studies have demonstrated essential roles for IRF3 and 111177, the definitive role of NF-kappa B factors in IFN-beta (or IFN-a) expression remains unknown. Using mice deficient in distinct members of the NF-kappa B family, we investigated NF-kappa B function in regulating type 1 IFN expression in response to Sendai virus and Newcastle disease virus infection. Surprisingly, IFN-beta and IFN-alpha expression was strongly induced following virus infection of mouse embryonic fibroblasts (MEFs) from p50(-/-), RelA/p65(-/-), cRel(-/-), p50(-/-) cRel(-/-), and p50(-/-)RelA(-/-) mice. Compared with wild-type MEFs, only RelA(-/-) and p50(-/-) RelA(-/-) MEFs showed a modest reduction in IFN-beta expression. To overcome functional redundancy between different NF-kappa B subunits, we expressed a dominant-negative I kappa Ba protein in p50(-/-)RelA(-/-) MEFs to inhibit activation of remaining NF-kappa B subunits. Although viral infection of these cells failed to induce detectable NF-kappa B activity, both Sendai virus and Newcastle disease virus infection led to robust IFN-beta expression. Virus infection of dendritic cells or TLR9-ligand CpG-D19 treatment of plasmacytoid dendritic cells from RelA(-/-) or p50(-/-)cRel(-/-) mice also induced robust type I IFN expression. Our findings therefore indicate that NF-KB subunits p50, RelA, and cRel play a relatively minor role in virus-induced type 1 IFN expression.