Differential type IIFN-Inducing abilities of wild-type versus vaccine strains of measles virus
Differential type IIFN-Inducing abilities of wild-type versus vaccine strains of measles virus
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DOI：
10.4049/jimmunol.179.9.6123
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Seya, Tsukasa
中科院分区：
文献类型：
--
作者：
Shingai, Masashi;Ebihara, Takashi;Seya, Tsukasa
麻疹病毒（MV）的实验室适应株和疫苗株在感染细胞中诱导I型IFN。相比之下，野生型菌株诱导的程度要小得多。我们已经研究了这种差异I型干扰素诱导单核细胞来源的树突状细胞感染的代表性MV菌株的机制。实验室适应菌株Nagahata和Edmonston感染单核细胞衍生的树突状细胞并激活IRF-3，随后产生IFN-γ 6，而野生型MS未能激活IRF-3。病毒IRF-3激活在2小时内诱导，这是蛋白质合成前发生的早期反应。CD 46或CD 150的受体使用和核衣壳（N）蛋白的变化几乎没有影响菌株间IFN诱导能力的差异。引人注目的是，大多数IFN诱导菌株具有不同大小的缺陷干扰（DI）RNA。此外，人工产生的DI RNA由茎（MV的前导和尾部）和环（GFP序列）组成，表现出潜在的IFN诱导能力。然而，在这种情况下，需要细胞质引入DI RNA以在靶细胞中诱导I型IFN。通过基因沉默分析，DI RNA激活RIG-IIMDA 5-线粒体抗病毒信号通路，但不激活TLR 3-TICAM-1通路。含有DI RNA的菌株在2小时内诱导IFN-β mRNA，而不含DI RNA的相同重组菌株需要>12小时感染后才能达到类似的IFN-β mRNA水平。因此，茎环结构，而不是完整的基因组复制或特定的MV基因组的内部序列，是需要的I型IFN诱导MV在宿主细胞中的早期阶段。
Laboratory adapted and vaccine strains of measles virus (MV) induced type I IFN in infected cells. The wild-type strains in contrast induced it to a far lesser extent. We have investigated the mechanism for this differential type I IFN induction in monocyte-derived dendritic cells infected with representative MV strains. Laboratory adapted strains Nagahata and Edmonston infected monocyte-derived dendritic cells and activated IRF-3 followed by IFN-,6 production, while wild-type MS failed to activate IRF-3. The viral IRF-3 activation is induced within 2 h, an early response occurring before protein synthesis. Receptor usage of CD46 or CD150 and nucleocapsid (N) protein variations barely affected the strain-to-strain difference in IFN-inducing abilities. Strikingly, most of the IFN-inducing strains possessed defective interference (DI) RNAs of varying sizes. In addition, an artificially produced DI RNA consisting of stem (the leader and trailer of MV) and loop (the GFP sequence) exhibited potential IFN-inducing ability. In this case, however, cytoplasmic introduction was needed for DI RNA to induce type I IFN in target cells. By genesilencing analysis, DI RNA activated the RIG-IIMDA5-mitochondria antiviral signaling pathway, but not the TLR3-TICAM-1 pathway. DI RNA-containing strains induced IFN-beta mRNA within 2 h while the same recombinant strains with no DI RNA required >12 h postinfection to attain similar levels of IFN-beta mRNA. Thus, the stem-loop structure, rather than full genome replication or specific internal sequences of the MV genome, is required for an early phase of type I IFN induction by MV in host cells.