Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons
Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons
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黄热病病毒感染细胞产生的未成熟颗粒和无衣壳病毒RNA刺激浆细胞样树突状细胞分泌干扰素
作者：
L. Sinigaglia;Ségolène Gracias;Elodie Décembre;Matthieu Fritz;Daniela Bruni;Nikaïa Smith;J. Herbeuval;Annette Martin;M. Dreux;F. Tangy;N. Jouvenet
浆细胞样树突状细胞（pDCs）在应对病毒感染时专门产生干扰素（ifn）。黄病毒科包括包膜RNA病毒，如丙型肝炎病毒（HCV）和登革热病毒（DENV）。无细胞黄病毒科病毒体很难刺激pDCs产生IFN。相比之下，感染HCV和DENV的细胞通过短程递送病毒rna（包装在未成熟病毒粒子或分泌的外泌体中）有效地刺激pDCs。我们报道了感染了典型黄病毒黄热病病毒（YFV）的细胞，刺激pDCs以TLR7和细胞接触依赖的方式产生ifn。这种刺激不受YFV中和抗体存在的影响。据报道，对于DENV，产生未成熟YFV颗粒的细胞比释放成熟病毒粒子的细胞更能刺激pDCs。此外，复制释放缺陷的YFV突变体或缺乏结构蛋白编码序列的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通过至少两种机制到达pDCs：在未成熟颗粒内和作为无衣壳rna。我们的工作强调了pDCs对受感染细胞产生的各种病毒rna负载载体的反应能力。
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.
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影响因子：
16.8
作者：
Hoffmann HH;Schneider WM;Rice CM
通讯作者：
Rice CM
影响因子：
15.9
作者：
Beignon, AS;McKenna, K;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
30.3
作者：
Dreux M;Garaigorta U;Boyd B;Décembre E;Chung J;Whitten-Bauer C;Wieland S;Chisari FV
通讯作者：
Chisari FV
DOI：
10.1073/pnas.0400937101
发表时间：
2004-04-13
影响因子：
11.1
作者：
Lund, JM;Alexopoulou, L;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
5.9
作者：
Pierson, Theodore C.;Diamond, Michael S.
通讯作者：
Diamond, Michael S.