Lethal Nipah virus infection induces rapid overexpression of CXCL10.
Lethal Nipah virus infection induces rapid overexpression of CXCL10.
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DOI：
10.1371/journal.pone.0032157
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Horvat B
中科院分区：
文献类型：
--
作者：
Mathieu C;Guillaume V;Sabine A;Ong KC;Wong KT;Legras-Lachuer C;Horvat B
尼帕病毒（Nipah virus，NiV）是一种新近发现的人畜共患副粘病毒，在东亚地区经常暴发流行，死亡率超过75%。NiV感染的主要细胞靶标是内皮细胞和神经元。为了更好地理解病毒-宿主相互作用，我们分析了NiV感染原代人脐静脉内皮细胞的转录组谱。我们进一步评估了在仓鼠模型和NiV感染患者的脑样品中通过体外和体内方法获得的一些结果。我们发现NiV感染强烈诱导内皮细胞中参与干扰素应答的基因。在前十名上调的基因中，我们确定了趋化因子CXCL 10（干扰素诱导蛋白10，IP-10），一种重要的化学引诱物，参与炎症免疫反应和神经毒性的产生。在NiV感染的仓鼠中，其发展的病理学类似于在人类中看到的，在不同器官中诱导CXCL 10 mRNA的表达，其动力学遵循NiV复制。最后，我们在马来西亚爆发期间死于致命NiV感染的患者的大脑中显示了CXCL 10的强烈染色，证实了这种趋化因子在致命人类感染中的诱导作用。这项研究揭示了NiV的发病机制，表明CXCL 10在感染过程中的作用，并表明这种趋化因子可能作为致命NiV脑炎的潜在新标志物。
Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.