Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA
Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA
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DOI：
10.1038/ncomms2857
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发表时间：
2013-05-01
影响因子：
16.6
通讯作者：
Matsumoto, Misako
中科院分区：
文献类型：
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作者：
Tatematsu, Megumi;Nishikawa, Fumiko;Matsumoto, Misako
内体toll样受体3 （TLR3）作为病毒感染和无菌组织坏死的传感器。尽管TLR3识别双链RNA，但在感染/炎症状态下激活TLR3的病毒或宿主来源的RNA的结构特征知之甚少。在这里，我们证明脊髓灰质炎病毒衍生的单链RNA片段含有凸起/内部环的茎结构，是有效的TLR3激动剂。功能性脊髓灰质炎病毒rna耐降解，并以tlr3依赖的方式在人和小鼠细胞中有效诱导干扰素- α / β和促炎细胞因子。TLR3的N和c端双链rna结合位点是脊髓灰质炎病毒rna介导的TLR3激活所必需的。像polyriboinosic:polyribocytidylic acid，一种合成的双链RNA一样，这些RNA通过raft介导的内吞作用被内化到细胞中，并与TLR3共定位。raftlin相关的RNA摄取机制和TLR3 RNA传感系统似乎可以识别脊髓灰质炎病毒RNA中多个RNA双链的适当拓扑结构。因此，TLR3是细胞外病毒/宿主RNA的传感器，其稳定的茎结构来源于感染或炎症损伤的细胞。
Endosomal Toll-like receptor 3 (TLR3) serves as a sensor of viral infection and sterile tissue necrosis. Although TLR3 recognizes double-stranded RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. Here we demonstrate that poliovirus-derived single-stranded RNA segments harbouring stem structures with bulge/internal loops are potent TLR3 agonists. Functional poliovirus-RNAs are resistant to degradation and efficiently induce interferon-alpha/beta and proinflammatory cytokines in human and mouse cells in a TLR3-dependent manner. The N- and C-terminal double-stranded RNA-binding sites of TLR3 are required for poliovirus-RNA-mediated TLR3 activation. Like polyriboinosinic:polyribocytidylic acid, a synthetic double-stranded RNA, these RNAs are internalized into cells via raftlin-mediated endocytosis and colocalized with TLR3. Raftlin-associated RNA uptake machinery and the TLR3 RNA-sensing system appear to recognize an appropriate topology of multiple RNA duplexes in poliovirus-RNAs. Hence, TLR3 is a sensor of extracellular viral/host RNA with stable stem structures derived from infection or inflammation-damaged cells.