Abstract

BackgroundJapanese 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.ResultsThe 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.ConclusionsData 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.

Highlights

  • Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, leading to an acute encephalitis and damage to the central nervous system (CNS)

  • Results mRNA expression profile of JEV-infected mice A mouse whole gene array was used to perform a systematic analysis of mRNA expression profile of spleen and brain tissues of JEV P3-infected mice which were sacrificed at day 3 and day 6 post-inoculation respectively

  • Of 41174 genes represented on the chip, 437 genes were differentially expressed in mouse spleens and 1119 genes were differentially regulated in brains in response to JEV infection

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Summary

Introduction

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, leading to an acute encephalitis and damage to the central nervous system (CNS). Japanese encephalitis virus (JEV), a mosquito-borne flavivirus belonging to family Flaviviridae, is responsible for an acute encephalitis and damage to the central nervous system (CNS) in wide areas of southern and eastern Asia. Recently, it has been isolated from previously non-affected areas, such as Australia [1]. Identification of gene profiles in JEV-infected neuroblastoma cells and brain tissue have been reported recently, suggesting an increased expression of pro-inflammatory cytokines, chemokines, and anti-viral response genes after JEV infection [11,12]. Both of studies on JEV were restricted to CNS, and few gene profiling researches about response in peripheral immune system has been carried out

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