Activation of interferon response through toll-like receptor 3 impacts viral pathogenesis and pulmonary toll-like receptor expression during respiratory syncytial virus and influenza infections in the cotton rat Sigmodon hispidus model.
Activation of interferon response through toll-like receptor 3 impacts viral pathogenesis and pulmonary toll-like receptor expression during respiratory syncytial virus and influenza infections in the cotton rat Sigmodon hispidus model.
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DOI：
10.1089/jir.2009.0025
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Blanco JC
中科院分区：
文献类型：
--
作者：
Boukhvalova MS;Sotomayor TB;Point RC;Pletneva LM;Prince GA;Blanco JC
干扰素（IFN）治疗人类经常会引起流感样症状的一个未知的机制。Poly ICLC是一种合成的dsRNA和具有强IFN诱导能力的Toll样受体3（TLR 3）激动剂。在这项工作中，我们分析了聚ICLC对棉鼠（S。hispidus）模型。病毒复制，肺部炎症，IFN，TLR和趋化因子的表达进行了监测和比较。聚ICLC对流感病毒和RSV的抗病毒作用在高聚ICLC浓度下达到最佳，在不存在病毒感染的情况下，诱导强烈的IFN应答。然而，聚ICLC的抗病毒剂量也增加了肺部炎症，这是一个意外的发现，因为报告了聚ICLC在BALB/c小鼠中的安全性。类似地，与鼠模型相反，用聚ICLC处理的棉鼠中RSV感染的病理学增加。增强的肺部炎症伴随着更早的IFN和TLR反应的诱导和更强的趋化因子表达。总体而言，这些发现表明抗病毒IFN作用和肺部炎症之间存在显著关联，并突出了IFN引起病理学的可能性的重要动物模型特异性变化。
Interferon (IFN) therapy in humans often causes flu-like symptoms by an unknown mechanism. Poly ICLC is a synthetic dsRNA and a toll-like receptor 3 (TLR3) agonist with a strong IFN-inducing ability. In this work we analyzed the effect of poly ICLC on pulmonary responses to influenza and Respiratory Syncytial Virus (RSV) infections in the cotton rat (S. hispidus) model. Viral replication, pulmonary inflammation, and expression of IFN, TLR, and chemokines were monitored and compared. Antiviral effect of poly ICLC against influenza virus and RSV was best achieved at high poly ICLC concentrations that, in the absence of virus infection, induced a strong IFN response. The antiviral doses of poly ICLC, however, also increased lung inflammation, an unexpected finding because of the reported poly ICLC safety in BALB/c mice. Similarly, in contrast to murine model, pathology of RSV infection was increased in cotton rats treated with poly ICLC. Augmented lung inflammation was accompanied by an earlier induction of IFN and TLR responses and a stronger chemokine expression. Overall, these findings indicate significant association between antiviral IFN action and pulmonary inflammation and highlight important animal model-specific variations in the potential of IFN to cause pathology.
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影响因子：
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作者：
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