Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner. Such stimulation was unaffected by the presence of YFV neutralizing antibodies. As reported for DENV, cells producing immature YFV particles were more potent at stimulating pDCs than cells releasing mature virions. Additionally, cells replicating a release-deficient YFV mutant or a YFV subgenomic RNA lacking structural protein-coding sequences participated in pDC stimulation. Thus, viral RNAs produced by YFV-infected cells reach pDCs via at least two mechanisms: within immature particles and as capsid-free RNAs. Our work highlights the ability of pDCs to respond to a variety of viral RNA-laden carriers generated from infected cells.

中文翻译：

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黄热病病毒感染的细胞产生的未成熟颗粒和无衣壳的病毒RNA刺激浆细胞样树突状细胞分泌干扰素。

浆细胞样树突状细胞（pDC）专用于响应病毒感染而产生干扰素（IFN）。黄病毒科包括包膜RNA病毒，例如丙型肝炎病毒（HCV）和登革热病毒（DENV）。无细胞的黄病毒科病毒粒子很难刺激pDC产生IFN。相比之下，感染HCV和DENV的细胞可通过短距离递送病毒RNA来有效刺激pDC，后者可包装在未成熟的病毒体中或分泌的外泌体中。我们报告说，感染黄热病病毒（YFV），原型黄病毒的细胞刺激pDC以TLR7和细胞接触依赖性方式产生IFN。此类刺激不受YFV中和抗体的影响。根据DENV的报道，产生不成熟YFV颗粒的细胞比释放成熟病毒体的细胞在刺激pDC方面更有效。另外，复制缺少结构蛋白编码序列的缺乏释放的YFV突变体或YFV亚基因组RNA的细胞参与了pDC刺激。因此，由YFV感染的细胞产生的病毒RNA至少通过两种机制到达pDC：未成熟颗粒内和无衣壳RNA。我们的工作强调了pDC对被感染细胞产生的多种病毒RNA携带者产生应答的能力。