Interleukin-34 Inhibits Hepatitis B Virus Replication

ObjectiveTo study the role of IL-34 in HBV replication process.Methods1.The serum concentrations of total protein,albumin,alkanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB),direct bilirubin(DB)and alpha-fetoprotein(AFP)between chronic HBV patient group and the healthy control group were compared.2.The expression level of IL-34 in chronic HBV patients and healthy controls was analyzed by ELISA and qRT-PCR.The effect of HBV replication on the expression of IL-34 was determined by qRT-PCR and ELISA in HBV-expressing cells.3.The correlations of clinical parameters with IL-34 levels were analyzed.4.HBV-expressing cells were treated with different concentrations of rhIL-34,and then the level of HBV DNA replicative intermediates was analyzed by real-time PCR and Southern blotting;Total RNA and 3.5kb mRNA were determined by q RT-PCR;HBV core protein level was analyzed by Western blotting.5.HBV transgenic mice were injected with rhIL-34 via tail vein.The level of serums HBV DNA was determined by real-time PCR.The level of HBV DNA?total RNA and 3.5 kb mRNA in mouse liver tissues were determined by qRT-PCR.HBV core protein level was analyzed by Western blotting.Results1.The serum concentrations of alkanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB),direct bilirubin(DB)and alpha-fetoprotein(AFP)were significantly elevated in chronic HBV patient group compared to the healthy control group,but total protein and albumin were significantly decreased in chronic HBV patient group.2.IL-34 level decreased in chronic HBV patients relative to healthy controls.The HBV replication inhibited the expression of IL-34 in HBV-expressing cells.3.The level of serum IL-34 negatively correlated with the serum level of HBV DNA?ALT?AST.4.IL-34 inhibited the expression of HBV DNA replicative intermediates?total RNA and 3.5 kb mRNA and HBV core protein in HBV-expressing cells.5.IL-34 inhibited the replication of HBV in HBV transgenic mice.Conclusion These data suggest that IL-34 inhibits HBV replication.