Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA

Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
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DOI:
10.1126/science.1093616
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发表时间:
2004-03-05
期刊:
影响因子:
56.9
通讯作者:
Sousa, CRE
Sousa, CRE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Diebold, SS;Kaisho, T;Sousa, CRE

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干扰素(IFN)是保护免受病毒感染的关键,但连接病毒识别IFN诱导的途径仍然知之甚少。浆细胞样树突状细胞产生大量的IFN-α以响应野生型流感病毒。在这里,我们表明,这需要内体识别流感基因组RNA和信号转导的Toll样受体7(TLR 7)和MyD 88。非病毒来源的单链RNA(ssRNA)分子也诱导TLR 7依赖性炎症细胞因子的产生。这些结果将ssRNA鉴定为TLR 7的配体,并表明先天免疫系统的细胞感知内体ssRNA以检测RNA病毒的感染。
Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.