Insights into Human Astrocyte Response to H5N1 Infection by Microarray Analysis.

Insights into Human Astrocyte Response to H5N1 Infection by Microarray Analysis.
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DOI:
10.3390/v7052618
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发表时间:
2015-05-22
期刊:
Viruses
影响因子:
--
通讯作者:
Jin M
Jin M
中科院分区:
其他
文献类型:
--
作者:
Lin X;Wang R;Zhang J;Sun X;Zou Z;Wang S;Jin M

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流感病毒不仅感染呼吸系统,还感染中枢神经系统(CNS),导致流感相关脑病和脑炎。星形胶质细胞对于大脑稳态和神经元功能至关重要。这些细胞也可能被流感病毒感染。然而,星形胶质细胞响应流感病毒感染的全基因组变化尚未确定。在这项研究中,我们对人类星形胶质细胞针对 H5N1 病毒的反应进行了基因分析。先天免疫和促炎反应在感染后 24 小时 (hpi) 被强烈激活。抗病毒基因以及多种细胞因子和趋化因子(包括 CXCL9、CXCL10 和 CXCL11)均被强烈诱导。 p65 和 p38 的磷酸化可被病毒感染激活,表明它们在 H5N1 诱导的促炎症反应中具有潜在的关键作用。此外,H5N1感染在感染后24小时显着上调与神经活性配体-受体相互作用途径相关的基因表达,如MC2R、CHRNG、P2RY13、GABRA1和HRH2,这些基因参与突触传递,可能参与H5N1感染引起的中枢神经系统疾病。针对先天免疫反应的关键成分和神经活性配体-受体相互作用途径可能提供控制 H5N1 诱发的脑病和脑炎的策略。这项研究有助于了解星形胶质细胞中 H5N1 的发病机制。
Influenza virus infects not only the respiratory system but also the central nervous system (CNS), leading to influenza-associated encephalopathy and encephalitis. Astrocytes are essential for brain homeostasis and neuronal function. These cells can also be infected by influenza virus. However, genome-wide changes in response to influenza viral infection in astrocytes have not been defined. In this study, we performed gene profiling of human astrocytes in response to H5N1. Innate immune and pro-inflammatory responses were strongly activated at 24 h post-infection (hpi). Antiviral genes, as well as several cytokines and chemokines, including CXCL9, CXCL10, and CXCL11, were robustly induced. Phosphorylation of p65 and p38 can be activated by viral infection, suggesting their potential critical roles in H5N1-induced pro-inflammatory response. Moreover, H5N1 infection significantly upregulated the gene expressions related to the neuroactive ligand-receptor interaction pathway at 24 hpi, such as MC2R, CHRNG, P2RY13, GABRA1, and HRH2, which participant in synaptic transmission and may take part in CNS disorders induced by H5N1 infection. Targeting key components of innate immune response and the neuroactive ligand-receptor interaction pathway may provide a strategy to control H5N1-induced encephalopathy and encephalitis. This research can contribute to the understanding of H5N1 pathogenesis in astrocytes.
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