IRF3 mediates a TLR3/TLR4-specific antiviral gene program
IRF3 mediates a TLR3/TLR4-specific antiviral gene program
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DOI：
10.1016/s1074-7613(02)00390-4
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发表时间：
2002-09-01
期刊：
影响因子：
32.4
通讯作者：
Cheng, G
中科院分区：
文献类型：
--
作者：
Doyle, SE;Vaidya, SA;Cheng, G
我们已经确定了一个基因的子集，该子集是由TLR3或TLR4刺激而不是由TLR2或TLR9刺激的。进一步的基因表达分析表明，几个主要反应基因的上调取决于NF-kappab，通常由几个TLR激活，而干扰素调节因子3（IRF3）被发现赋予TLR3/TLR4特异性。还确定的是一组二级反应基因，该基因是由主要反应基因产物Interferon beta（IFNBETA）激活的自分泌/旁分泌环的一部分。 TLR3/TLR4-IRF3途径的选择性激活有效抑制病毒复制。这些结果表明，TLR3和TLR4在进化上与其他TLR分歧以激活IRF3，该IRF3介导了负责先天抗病毒反应的特定基因程序。
We have identified a subset of genes that is specifically induced by stimulation of TLR3 or TLR4 but not by TLR2 or TLR9. Further gene expression analyses established that upregulation of several primary response genes was dependent on NF-kappaB, commonly activated by several TLRs, and interferon regulatory factor 3 (IRF3), which was found to confer TLR3/TLR4 specificity. Also identified was a group of secondary response genes which are part of an autocrine/paracrine loop activated by the primary response gene product, interferon beta (IFNbeta). Selective activation of the TLR3/TLR4-IRF3 pathway potently inhibited viral replication. These results suggest that TLR3 and TLR4 have evolutionarily diverged from other TLRs to activate IRF3, which mediates a specific gene program responsible for innate antiviral responses.