The nitric oxide pathway provides innate antiviral protection in conjunction with the type I interferon pathway in fibroblasts.
The nitric oxide pathway provides innate antiviral protection in conjunction with the type I interferon pathway in fibroblasts.
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DOI：
10.1371/journal.pone.0031688
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mossman KL
中科院分区：
文献类型：
--
作者：
Mehta DR;Ashkar AA;Mossman KL
对病毒感染的先天宿主应答主要由I型干扰素和干扰素刺激基因的产生主导。特别是，成纤维细胞对病毒感染和病毒特征（如dsRNA）的识别有强烈的反应，并快速产生I型干扰素;因此，成纤维细胞是抗病毒保护中的关键细胞类型。然而，我们最近发现，干扰素、干扰素刺激基因和其他细胞因子和趋化因子的产生缺陷的原代成纤维细胞在用dsRNA刺激后产生针对DNA和RNA病毒的强抗病毒应答。一氧化氮是一种具有多效性功能的化合物;吞噬细胞对干扰素-γ产生的一氧化氮与抗菌活性有关。在这里，我们表明，为了响应双链RNA，原代成纤维细胞中迅速产生一氧化氮。在存在完整的干扰素系统的情况下，一氧化氮在抗病毒保护中起次要但重要的作用。然而，在没有干扰素系统的情况下，一氧化氮对于保护免受DNA病毒的侵害至关重要。在原代成纤维细胞中，NF-κB和干扰素调节因子1参与诱导型一氧化氮合酶表达的诱导，其随后产生一氧化氮。由于大型DNA病毒编码多种多样的免疫调节剂以使干扰素系统失效，因此似乎一氧化氮途径作为保护宿主免受关键细胞类型（如成纤维细胞）中的病毒感染的次要策略，所述关键细胞类型主要依赖I型干扰素系统进行抗病毒保护。
The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, however, that primary fibroblasts deficient for the production of interferon, interferon stimulated genes, and other cytokines and chemokines mount a robust antiviral response against both DNA and RNA viruses following stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic functions; its production by phagocytes in response to interferon-γ is associated with antimicrobial activity. Here we show that in response to dsRNA, nitric oxide is rapidly produced in primary fibroblasts. In the presence of an intact interferon system, nitric oxide plays a minor but significant role in antiviral protection. However, in the absence of an interferon system, nitric oxide is critical for the protection against DNA viruses. In primary fibroblasts, NF-κB and interferon regulatory factor 1 participate in the induction of inducible nitric oxide synthase expression, which subsequently produces nitric oxide. As large DNA viruses encode multiple and diverse immune modulators to disable the interferon system, it appears that the nitric oxide pathway serves as a secondary strategy to protect the host against viral infection in key cell types, such as fibroblasts, that largely rely on the type I interferon system for antiviral protection.
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影响因子：
14
作者：
Charville, Gregory W.;Hetrick, Evan M.;Geer, Carri B.;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.
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作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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Wietzerbin, J