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病毒缺陷干扰颗粒在增强树突状细胞成熟过程中的新作用。

A novel role for viral-defective interfering particles in enhancing dendritic cell maturation.

作者信息

Yount Jacob S, Kraus Thomas A, Horvath Curt M, Moran Thomas M, López Carolina B

机构信息

Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

出版信息

J Immunol. 2006 Oct 1;177(7):4503-13. doi: 10.4049/jimmunol.177.7.4503.

Abstract

Dendritic cell (DC) maturation is a crucial event in the development of adaptive immune responses that confer long-lasting protection against reinfection with the same virus. Sendai virus strain Cantell has a particularly strong ability to mature DCs independently of type I IFNs and TLR signaling, currently the best-described pathways for the induction of DC maturation. In this study, we demonstrate that defective-interfering (DI) particles present in Sendai virus-Cantell stocks are required for its robust DC maturation ability. DI particles contain incomplete genomes that are unable to replicate unless the viral polymerase is supplied by coinfection with complete virus. Accordingly, the improvement in the virus-induced maturation of DCs provided by DI particles requires standard virus coinfection and likely results from increased production of dsRNA replication intermediaries. This unique ability of DI particles to stimulate DC maturation cannot be mimicked by simply increasing the dose of standard virus. Furthermore, viruses with weak DC maturation abilities can be converted into potent DC stimulators with the addition of DI particles, supporting a potential application for DI particles as a novel natural adjuvant for viral immunizations.

摘要

树突状细胞(DC)成熟是适应性免疫反应发展过程中的一个关键事件,这种免疫反应能提供针对同一病毒再次感染的持久保护。仙台病毒坎特尔株具有特别强大的能力,可独立于I型干扰素和Toll样受体(TLR)信号传导使DC成熟,而I型干扰素和TLR信号传导是目前描述得最为清楚的诱导DC成熟的途径。在本研究中,我们证明了仙台病毒 - 坎特尔毒株储备中存在的缺陷干扰(DI)颗粒是其强大的DC成熟能力所必需的。DI颗粒包含不完整的基因组,除非通过与完整病毒共感染提供病毒聚合酶,否则它们无法复制。因此,DI颗粒所带来的病毒诱导的DC成熟的改善需要标准病毒共感染,并且可能是由于双链RNA复制中间体产量增加所致。DI颗粒刺激DC成熟的这种独特能力无法通过简单增加标准病毒剂量来模拟。此外,添加DI颗粒可将DC成熟能力较弱的病毒转化为强大的DC刺激剂,这支持了DI颗粒作为病毒免疫新型天然佐剂的潜在应用。

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