Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems
Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems
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DOI：
10.1128/jvi.01167-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Paludan, Soren R.
中科院分区：
文献类型：
--
作者：
Rasmussen, Simon B.;Sorensen, Louise N.;Paludan, Soren R.
先天免疫系统的种系编码的模式识别受体识别病毒对于I型干扰素（IFN）的快速产生和早期抗病毒防御是必不可少的。我们研究了单纯疱疹病毒（HSV）感染过程中病毒识别调控I型IFN产生的机制。我们表明，早期生产的干扰素在体内介导的Toll样受体9（TLR 9）和浆细胞样树突状细胞，而随后的α/β干扰素（IFN-α/β）的反应是来自几种细胞类型和诱导独立的TLR 9。在传统的DC中，IFN应答独立于病毒复制而发生，但依赖于病毒进入。此外，使用HSV-1 UL 15突变体，它不能将病毒DNA包装到病毒体中，我们发现，依赖于IFN的进入诱导也需要病毒基因组DNA的存在。在病毒能够复制的巨噬细胞和成纤维细胞中，HSV诱导的IFN-α/β 1产生依赖于病毒进入和复制，并且在不能通过线粒体抗病毒信号传导蛋白途径发出信号的细胞中被消除。因此，在体内HSV感染期间，病原体识别的多种机制是活跃的，其以细胞类型和时间依赖性方式操作以触发I型IFN的表达并协调抗病毒应答。
Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-alpha/beta) response is derived from several cell types and induced independently of TLR9. In conventional DCs, the IFN response occurred independently of viral replication but was dependent on viral entry. Moreover, using a HSV-1 UL15 mutant, which fails to package viral DNA into the virion, we found that entry-dependent IFN induction also required the presence of viral genomic DNA. In macrophages and fibroblasts, where the virus was able to replicate, HSV-induced IFN-a/(1 production was dependent on both viral entry and replication, and ablated in cells unable to signal through the mitochondrial antiviral signaling protein pathway. Thus, during an HSV infection in vivo, multiple mechanisms of pathogen recognition are active, which operate in cell-type- and time-dependent manners to trigger expression of type I IFN and coordinate the antiviral response.