在東南亞地區(qū),病毒性腦炎主要是由于JEV感染造成的。據(jù)報(bào)道每年有超過1.6萬(wàn)人的臨床病例,其中大致可導(dǎo)致5千人的死亡。2001-2010年期間,中國(guó)大陸的乙型腦炎病死率約為30%。近年來(lái),盡管乙腦疫苗的使用限制了疫病的暴發(fā),但是在某些發(fā)展中國(guó)家,乙型腦炎的地區(qū)性流行以及零星散發(fā)還很常見。實(shí)際上,并不是所有的JEV感染都可以導(dǎo)致腦炎,大多數(shù)情況下JEV感染并不引起腦炎。有數(shù)據(jù)顯示約300-1000的感染者中會(huì)出現(xiàn)1個(gè)腦炎的病例。因此,上述數(shù)據(jù)表明宿主的防御機(jī)制在病毒感染過程中發(fā)揮著重要的作用,即宿主的免疫防御反應(yīng)決定著病毒能否感染中樞神經(jīng)系統(tǒng)。相對(duì)于保護(hù)性的體液免疫,I型干擾素介導(dǎo)的先天性抗病毒作用在JEV感染中發(fā)揮著重要的作用,即限制病毒擴(kuò)散入腦并抑制其在中樞神經(jīng)中的感染。值得注意的是有些JEV毒株可以逃避這種I型干擾素介導(dǎo)的抗病毒反應(yīng)。除了逃避先天性抗病毒反應(yīng)外,乙型腦炎的產(chǎn)生與病毒誘發(fā)的炎性反應(yīng)不可分。這些病毒感染引起的炎性反應(yīng)不僅可以造成血腦屏障的損傷,而且還是導(dǎo)致神經(jīng)元細(xì)胞死亡的重要因素。然而目前,JEV是如何逃避I型干擾素介導(dǎo)的抗病毒反應(yīng)以及誘導(dǎo)炎性反應(yīng)的機(jī)制還有待進(jìn)一步研究...

【文章頁(yè)數(shù)】：51 頁(yè)

【學(xué)位級(jí)別】：碩士

【文章目錄】：
摘要
abstract
Chapter 1 Introduction
    1.1 Japanese encephalitis virus
    1.2 Significance and epidemiology-around the word
    1.3 Replication cycle of JEV
    1.4 Insights into pathogenesis of Japanese encephalitis
    1.5 Antiviral response of host’s innate immune system
    1.6 Invasion of native antiviral response of host
    1.7 Objective
Chapter 2 Proteomics Analysis of Mouse Brain Infected with JEV
    2.1 Introduction
    2.2 Materials and methods
        2.2.1 Ethical statement
        2.2.2 Animal model
        2.2.3 Inoculation of virus
        2.2.4 Collection of samples
        2.2.5 Cell culture
        2.2.6 Tissue culture infective dose
        2.2.7 iTRAQ-based proteomics analysis
            2.2.7.1 Protein extraction
            2.2.7.2 Protein digestion and iTRAQ labeling
            2.2.7.3 Peptide fractionation with strong cation exchange(SCX)chromatography
            2.2.7.4 Liquid chromatography(LC) –electrospray ionization(ESI)tandem MS(MS/MS)analysis by Q exactive
            2.2.7.5 Sequence database searching and data analysis
        2.2.8 Western blot
        2.2.9 Bioinformatics
        2.2.10 Primary neurons isolation
        2.2.11 Primary fibroblast isolation
        2.2.12 Typical RNAiMAX transfection procedure
    2.3 Results
        2.3.1 Mouse model;Infection,survival assay and harvest sheet for JEV infected mice
        2.3.2 Tissue culture infective dose
        2.3.3 Proteomic expression patterns in mouse brain after JEV infection
        2.3.4 Additional evidence validating the Mass Spectrometry data
        2.3.5 Up-regulation of ISG15 and B2M
        2.3.6 Down-regulation of AATK
        2.3.7 Gene ontology(GO)enrichment analysis of the DEPs by p value
        2.3.8 KEGG pathway enrichment analysis of differentially regulated proteins
        2.3.9 JEV infection upregulates expression of TREX
        2.3.10 Knock-down of TREX1 gene expression inhibits JEV infections
    2.4 Discussion
Chapter 3 Conclusions
References
Acknowledgements
Curriculum vitae



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