State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
Virol J. 2011 Feb 24;8:80. doi: 10.1186/1743-422X-8-80.
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, leading to an acute encephalitis and damage to the central nervous system (CNS). The mechanism of JEV pathogenesis is still unclear. DNA microarray analyses have been recently employed to detect changes in host gene expression, which is helpful to reveal molecular pathways that govern viral pathogenesis. In order to globally identify candidate host genes associated with JEV pathogenesis, a systematic mRNA profiling was performed in spleens and brains of JEV-infected mice.
The results of microarray analysis showed that 437 genes in spleen and 1119 genes in brain were differentially expressed in response to JEV infection, with obviously upregulated genes like pro-inflammatory chemokines and cytokines, apoptosis-related proteases and IFN inducible transcription factors. And the significant pathways of differentially expressed genes are involved in cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, antigen processing and presentation, MAPK signaling, and toll-like receptor signaling, etc. The differential expression of these genes suggests a strong antiviral response of host but may also contribute to the pathogenesis of JEV resulting in encephalitis. Quantitative RT-PCR (RT-qPCR) assay of some selected genes further confirmed the results of microarray assay.
Data obtained from mRNA microarray suggests that JEV infection causes significant changes of mRNA expression profiles in mouse spleen and brain. Most of differentially expression genes are associated with antiviral response of host, which may provide important information for investigation of JEV pathogenesis and therapeutic method.
日本脑炎病毒(JEV)是一种通过蚊子传播的黄病毒,可导致急性脑炎和中枢神经系统(CNS)损伤。JEV 发病机制的机制尚不清楚。最近已采用 DNA 微阵列分析来检测宿主基因表达的变化,这有助于揭示控制病毒发病机制的分子途径。为了全面鉴定与 JEV 发病机制相关的候选宿主基因,对 JEV 感染小鼠的脾脏和大脑进行了系统的 mRNA 谱分析。
微阵列分析的结果显示,脾脏中有 437 个基因和大脑中有 1119 个基因对 JEV 感染有差异表达,明显上调的基因如促炎趋化因子和细胞因子、凋亡相关蛋白酶和 IFN 诱导的转录因子。差异表达基因的显著途径涉及细胞因子-细胞因子受体相互作用、自然杀伤细胞介导的细胞毒性、抗原加工和呈递、MAPK 信号转导和 Toll 样受体信号转导等。这些基因的差异表达表明宿主具有强烈的抗病毒反应,但也可能导致 JEV 引起的脑炎发病机制。一些选定基因的定量 RT-PCR(RT-qPCR)检测进一步证实了微阵列检测的结果。
mRNA 微阵列获得的数据表明,JEV 感染可导致小鼠脾脏和大脑中 mRNA 表达谱发生显着变化。差异表达的大多数基因与宿主的抗病毒反应有关,这可能为 JEV 发病机制和治疗方法的研究提供重要信息。