The Mechanism Of The Induction Of PD-L1 By Hepatitis B Virus In Human Hepatocytes

Hepatitis B virus(HBV)is a kind of DNA virus,due to the precise regulation of its own life cycle and the specificity of the infected host,and its long-term latent and persistent infection,HBV has not found an effective way to eliminate the virus with the current technical means.At the same time,due to the interaction with the host in the process of HBV infection,it has evolved a variety of immune suppression strategies.There are two major immune systems in the human body: innate immunity and acquired immunity,both of which play a very important role in the surveillance,defense and clearance of HBV.On the one hand,HBV can interact with multiple signal molecules in the innate immune signal pathway through envelope proteins such as HBV X protein,(HBx),HBV S antigen,(HBs Ag),HBV e antigen(HBe Ag)and HBV core protein(HBc Ag),so as to evade the killing effect of interferon on itself and promote the infection of other viruses to the host.On the other hand,HBV can regulate the expression of a variety of immune detection molecules in infected cells,thus affecting the immune surveillance and killing of NK cells and T cells.The signal transduction pathway regulated by axis inhibitory protein(Axin)and PD-L1 play a very important role in the growth and development of organisms.Some viruses and tumors can use them for immune escape.Axin,as a key regulatory protein in the signal transduction pathway,plays an important role in the signal transduction pathway.Through research,we found that Axin and PD-L1 also play an important role in the immune escape of HBV.The main purpose of this study is to explore the specific mechanism of HBV evading immune surveillance and immune killing.In this study,we discussed the mechanism of HBV regulating the expression of PD-L1 in hepatocytes.We found that HBV infection had no effect on the m RNA levels of Axin and PD-L1 in hepatocytes,but could down-regulate the level of Axin protein and up-regulate the level of PD-L1 protein in hepatocytes.On this basis,we overexpressed 1.3fold replicators of HBV in hepatocytes,and we found that there was still no effect on Axin and PD-L1 at the m RNA level,while at the protein level,compared with the control group,Axin protein was down-regulated and PD-L1 protein was up-regulated.On the other hand,because HBx plays an important role in the life cycle of HBV and in the process of HBV infecting the host,we explored it.Compared with the control group,we found that HBx down-regulated the expression of Axin and up-regulated PD-L1 in hepatocytes.Therefore,we speculate that there is a certain causal relationship between this phenomenon,so we overexpress Axin,in hepatocytes stably infected with HBV.The results show that overexpression of Axin can reverse the upregulation of PD-L1.Through the preliminary study,we found that Axin can regulate the expression of PD-L1.Therefore,we discussed the specific mechanism of the effect of Axin on PD-L1.Through verification at the levels of transcription,translation and post-translation,we found that overexpression of Axin could affect the ubiquitin degradation process of PD-L1,and then we conducted a preliminary study on the process of deubitization and ubiquitin of PD-L1.We found that overexpression of Axin upregulated the protein level of E3 ubiquitin ligase SPOP of PD-L1,and then down-regulated the protein level of PD-L1.Further study found that Axin promoted the K48-dependent ubiquitin degradation of PD-L1.Based on the above results,we suggest that HBV may down-regulate the levels of Axin and SPOP proteins through X protein(HBx),inhibit the ubiquitin degradation of PD-L1,and escape the host immune response.This study reveals a new mechanism of HBV immune escape and provides a new prospect for exploring the treatment of HBV.