干扰素诱导的dai蛋白抑制乙型肝炎病毒复制的初步分析

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1、硕士学位论文中文摘要干扰素产生的诱导。以上发现丰富了对干扰素抗病毒作用机制的认识，为HBV感染的治疗提供了新的思路和实验基础。关键词:乙型肝炎病毒;干扰素;DNA依赖的干扰素调节因子激活蛋白(DAI);抗病毒活性;核因子kappaB(NF一KB);中图分类号:R373.2+l硕士学位论文英文摘要Interferon一indueibleDAIProteininhibitsHePatitisBvirusrePlieationHePatitisBvirusinfection15aglobalPublichealthProblem，withover

2、300millionPeoPleworldwidebeingehronieHBVearriersandmillionsofdeathsannuallyattributabletoHBVrelatedliverfailure(eirrhosisorhePatoeellulareareinoma).Asasecretedcytokinethatelieitsdistinctantiviraleffeet，interferon(IFN)hasbeenusedfortreatmentofehronieHBVinfectionformorethant

3、wodeeades，yetthemechanismofactionofthisantiviralremainsPoorlyunderstood.PreviousstudieshaveProvedthatanti一virusactionofinterferon15mediatedbytheinduetionofanti一virusProtein，PlentyofgenesareregulatedbyIFN，forexamPle，2，，5’一oligoadenylatesynthetase，ProteinkinaseR，andMxAandthe

4、seProductsarethekeymediatorsofIFN’santiviralresPonse.AlthoughPreviousstudieshavebeendemonstratedthatafewofIFN一inducibleProteinseouldexertanti一HBVeffeetI’nvitr口orinvivo，suchasAPoBEC3，MXAandMyD88，theystilleouldnotfullyaccountforIFN’5effectonHBVrePlieation.Hence，otherIFNinduc

5、edProtein(s)mightalsobeinvolvedintheinhibitionofHBVrePlieationbyIFN.DAI(DLM一l/ZBPI)wasinitiallyidentifiedasahighlyeonservedRNA一bindingProtein，whichcouldbindtotheziPeodemotifofp一actinmRNAandthereforeberesPonsibleforitsintracellularlocalizationandcellPolarity.FraneisV.Chisar

6、ietalhaverePortedthattheeXPressionlevelofDAI，5mRNAeouldbeuP一regulatedafterIFN一a/pandIFN一YstimulationinthehighlydifferentiatedhePatocyteHBVMet一4harboringHBVrePlieation.In2007，TadadsuguTaniguchietalhavedemonstratedthatDAIeouldsignifieantlyindueetheexPressionoftyPe1IFNthrough

7、bindingtoIRF3andTBKIasaDNAsensor.Therefore，it15quitePossiblethatDAImightroleintheinhibitionofHBVrePlieationexertedbytyPe1and11IFN，ToverifyDAIeanindueedbyinterferoninHumanHePatomaCellLine(Huh7)，wetreatHuh7cellswithdl月七rentdoseofinterferon一a.WefoundthatIFN一atreatmenteangreat

8、lyaetivateDAItranseriPtion.Todeterminetheanti一HBVeffectofDAIProtein，weeo一transfeetedHuh7h