Studies On The Interaction Between Host Restriction Factor BST-2and Hepatitis B Virus

Host restriction factor BST-2is an interferon-inducible antiviralglycoprotein. The study of BST-2becomes a hotspot of bioscience, sincethe restriction of BST-2in HIV-1releasing was discovered in2008. Themain function of BST-2is tethering the enveloped viruses at theinfectious cell membrane to inhibit the releasing. Hepatitis B Virus (HBV)is a enveloped Virus of hepadnaviridae，assembles at the multivesicularbodies(MVBs).HBV can cause acute and chronic infection and liverinflammation, which maybe develops cirrhosis, and an important factor ofhepatocellular carcinoma(HCC). In recent study, BST-2can also impactthe intracellular assembly and releasing at MVBs, where HBV assembles at.And whether BST-2regulates HBV production is largely unknown. So wedesigned the experiment to study the interaction between BST-2and HBV.According to the conclusion of recent research progresses, the projectof our experiment includes four aspects. The first one is the restrictionof HBV by BST-2variants, and the second one is the antagonism of HBVagainst BST-2, and the third one is the interaction between HBx and BST-2.Then, the last one is the regulation of NF-κB signal path by HBx and BST-2.Some definite results are demonstrated by analyzing the experimentaldata.In this study, HBV plasmid was transfected into hepatocyte andnon-hepatocyte, then protein expression was detected by western blot andHBV antigen by ELISA. It has been demonstrated the interaction betweenBST-2and HBV is in cell dependent fashion. In293T cells, BST-2producedby IFN-αinducible and transfection has a strong inhibition of HBV.However, exogenous BST-2has a weaker inhibition of HBV in Huh-7cells.Hepatocyte was transfected with HIV-1ΔVpu proviral plasmid and HBV orviral proteins plasmids, then the viruses in supernatant wereconcentrated by ultracentrifugation and detected by western blot. It is observed that HBV and HBx can promote the releasing of HIV ΔVpu, but itcan’t in non-hepatocyte, and Vpu cannot effectively recover theBST-2-induced restriction of HBV. And several BST-2variants havedifferent effects on the releasing of HBV and HIV-1. It is suggested thatthe antagonism towards BST-2between HBV and HIV-1is not similarcompletely.293T cells were transfected with HBx and BST-2plasmids, andcell proteins were detected by western blot. It is observed that BST-2is degraded by HBx. However, the proteases inhibitor was added aftertransfection and the degradation was inhibited. In hepatocyte, we findthat HBx causes the accumulation of BST-2, and the amount of BST-2is aried,without degradation. These results suggest the interaction between BST-2and HBx is also hepatocyte specific. The recent studies report that BST-2and HBx activate the NF-κB signal path respectively. In this paper, wetransfected the NF-κB report plasmid into hepatocyte and non-hepatocyte,and detected the luciferase activity. It has been demonstrated that BST-2activates the NF-κB signal both hepatocyte and non-hepatocyte, and theactivation of HBx in hepatocyte is not apparent and weak innon-hepatocyte.Although the BST-2-induced restriction and the mechanism of interactionbetween BST-2and HBV are not clear, some primary data has beendemonstrated in our researches, and suggest there is a link between thetwo. This maybe open up the field of the study that host cells resist HBVinfection, which may provide new targets for HBV clinical treatment.