Investigation On The Impact Of Hepatitis B Virus Infection On Serum Apolipoprotein A1, B And M Expression And The Underlying Molecular Mechanism

Human Hepatitis B virus (HBV) causes acute and chronic inflammation in human liver, eventually leading to liver fibrosis (LC) and hepatocellular carcinoma (HCC). Currently, the pathogenic and carcinogenic mechanism of HBV is not very clear.To further investigate the pathogenesis of HBV, we screened hepatoma cell line HepG2and HepG2.2.15cell lines using gene chip system for differentially expressed genes. The test results showed that apolipoprotein A1(ApoA1) and apolipoprotein protein B (ApoB) in HepG2.2.15was significantly lower than in HepG2cells, and apolipoprotein M (ApoM) expression was increased in HepG2.2.15cells. We further examined ApoA1, ApoB and ApoM serological levels in HBV patients and healthy controls. The results showed that, during HBV infection serological ApoAl and ApoB levels decreased significantly; ApoM significantly higher in patients with HBV.To investigate the mechanism underlying HBV regulation of ApoAl, we constructed the plasmid pApoAl-Luc which contains ApoAl gene promoter and luciferase reporter gene, and using RT-PCR and Western-blot to assess impact of HBV on ApoAl mRNA and protein expression, the results showed that HBVcould inhibit the expression of ApoA1at the promoter, mRNA and protein levels, and the effect was in dose-dependent manners.To investigate the mechanism underlying HBV regulation of ApoB, we transfected HepG2cells with pHBV1.3, and ApoB mRNA and protein expression were measured by RT-PCR and Western blotting. The results suggested that HBV can suppress ApoB expression in HepG2cells at mRNA and protein levels. Microsomal triglyceride transfer protein (MTP) is a regulatory protein of ApoB, and our results further suggested that HBV can inhibit MTP expression. Thus, HBV may inhibit the expression and secretion of ApoB via the inhibition of MTP expression.To investigate the impact of HBV on ApoM expression, we constructed a vector pAPOM-luc which contains ApoM promoter and luciferase reporter gene, to assess HBV regulation of ApoM gene promoter through the luciferase reporter system, and using RT-PCR and Western-blot to assess the impact of HBV on ApoM mRNA and protein expression. The results showed that HBV could affect ApoM expression at promoter, mRNA and protein levels, and ApoM can suppress HBV replication.In conclusion, this study explored the impact of HBV on ApoAl, ApoB and ApoM expression, and the mechanisms underlying the regulation, thus laid theoretical foundation for further research on the pathogenesis of HBV.