Study On The Role Of Encephalomyocarditis Virus 2C And 3A In Regulating RLR Signaling Pathway Through Heat Shock Protein 27

Heat shock protein 27 is a molecular chaperone protein that can widely participate in the host's antiviral response.It plays a pivotal role in stress response,virus proliferation,and tumor immunity.In order to study the effect of HSP27 on the proliferation of encephalomyocarditis virus and the RLR signal pathway activated.This thesis first explored the ways in which EMCV affects the expression of HSP27 and which viral protein of EMCV plays a major role in this process.Secondly,through the up-regulation and down-regulation of the expression of HSP27,the regulatory effect of HSP27 on EMCV proliferation was clarified.Finally,the effect of HSP27 on the RLR signaling pathway was verified,and the target proteins of the RLR signaling pathway that interact with HSP27 were screened through indirect immunofluorescence experiments and co-immunoprecipitation experiments,and finally provided new potential for the development of potential anti-EMCV infection virus drugs opinion.The findings are as follows:1.In A549 cells,EMCV does not affect the expression of HSP90?,GRP78 and HSP70,but can degrade HSP27 through autophagolysosome pathway.2.EMCV virus proteins 2C and 3A can degrade HSP27 through the autophagy-lysosomal pathway,and interact with HSP27 to co-localize in the cytoplasm.3.Transient and stable up-regulation of HSP27 can significantly inhibit EMCV proliferation;down-regulation of HSP27 can significantly promote EMCV proliferation,indicating that HSP27 plays a negative regulatory role in EMCV proliferation in vitro.4.HSP27 can positively regulate the activation of RLR signaling pathway by promoting the expression of RIG-I,MDA5,IRF3 and nuclear factor NF-?B subunit p65 and the nuclear transfer of IRF3 and p65.This article reveals for the first time that EMCV virus proteins 2C and 3A can degrade the host protein HSP27 through the autophagy-lysosome pathway to inhibit its promotion of the key linker molecules of RLR signaling pathway RIG-I,MDA5,IRF3 and p65 to antagonize the host cell immune response.In conclusion,this study explored the new role of 2C and 3A in EMCV in antagonizing host antiviral response,and clarified the molecular mechanism of HSP27 against EMCV infection,which will further clarify the discovery of EMCV immune escape mechanism and potential antiviral targets.Provided strong evidence.