天然免疫新分子eris的鉴定及相关抗病毒作用机制的分析-细胞生物学专业论文.docx

Identification and Characterization of ERIS，anEndoplasmic Reticulum IFN Stimulator and the Related Antiviral Signaling MechanismWenxiang Sun Cell BiologyDirected by Prof. Zhengfan Jiang, PhDAbstract:Innate immunity is the first line of host defense against the pathogens and exists in all animals, which plays a conserved and very important part in eliminating the invaded pathogens. In the past two decades, the researchers have realized that innate immunity acts as a key role in antiviral system. The innate immune system recognizes microorganisms through a set of germline-encoded pattern recognition receptors (PRRs), which activate the downstream signaling pathways and finally upregulates the production of type I interferon and inflammatory factors. PRRs mediated innate immune signaling pathways are strictly controlled by diversified molecule mechanisms which are not clearly clarified to date. For instance, the cytosolic innate immune signaling mediated by RNA and DNA viruses is not fully clarified, requiring the identification of novel genes involving in this process.To investigate the innate immune signaling pathway and seek the new members in innate immune system, we bulit up and performed a large-scale functional screening system using IFNβ, IFNα4 and IFNα8 promoter driving luciferase reportconstructs in VSV、LPS and ssRNA pretreated BMDM cDNA libraries. I successfullyidentified an innate immune novel gene ERIS as an ER strong IFN stimulator and a well known IFN activator IRF1, suggesting the screening system worked well.We found that ERIS overexpression strongly induced the production of type I interferon，IFN stimulated genes and inflammatory cytokines, which restricted the replication of viruses. Cytosolic DNA mediated production of type I interferon wascompletely abolished in Eris deficient cells. The DNA virus titer was much higher than in the WT or Mavs deficient cells, so ERIS mainly involved in the DNA-type I interferon pathway. ERIS has four transmembrane d