Ubiquitin Specific Protease 18 Inhibits The Anti-hepatitis B Virus Activity Of Interferon-alpha,But Does Not Affect Interferon-lambda In Hepg2.2.15 Cells

Objective:Chronic Hepatitis B(CHB)remains a serious global health problem,the low sustained virological response rate of interferon(IFN)is an important contributing factor.Ubiquitin specific protease 18(USP18)belongs to a group of interferon stimulated genes,our study aims to detect the effect of USP18 on interferon-alpha(IFNa)and interferon-lambda(IFNλ)mediated anti-hepatitis B virus(HBV)activity.Methods:Over expressing USP18 plasmid vector was transiently transfected into HepG2.2.15.The HepG2.2.15 were then treated with IFNa and IFNλ respectively.HBV was detected using western blotting,Real-time quantitative PCR(RT-qPCR)and Enzyme-linked Immunosorbent Assay(ELISA).Results:USP18 was successfully over expressed in the cells.In those cells expressing the USP18 construct the expression of hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),HBV-DNA and hepatitis B core antigen(HBcAg)were statistically lower than the pEGFP-N1 group with IFNa treatment,but there was little difference in the IFNλ treatment group.Similarly,the expression of MxA,ISG15 and IFIT1 in the pEGFP-USP18 group were all lower than the same genes in the pEGFP-N1 IFNα treatment group,but there was no observable difference in the IFNλ treatment group.Lastly,the p-stat1,STAT1 of JAK/STAT signaling pathway of the pEGFP-USP18 group was much lower the IFNa treated group,there was also no significant difference when compared to the IFNλ group.Conclusion:USP18 inhibits the activity and replication of IFNa during HBV infection by reducing the expression of the JAK-STAT signaling pathway.In contrast,USP18 has no effect on IFNλ during HBV infection throμgh inhibition of the JAK-STAT signaling pathway.