Heparan Sulfate D-glucosaminyl 3-O-Sulfotransferase3b1 Inhibit HBV Replication In Vitro

Hepatitis B virus infection is a worldwide epidemic disease. More than 350 million individuals worldwide suffer from chronic hepatitis B (CHB) infection, which is associated with a high risk of developing cirrhosis and hepatocellular carcinoma. Although the genome sequences of HBV are well established, little is known about its mechanism involved in liver damage and the associated liver diseases after HBV infection. Molecular mechanisms through which HBV infection and interaction between HBV and host factors remains unclear.Using cDNA microarray profiling analysis, we screened for gene expression patterns between HepG2.2.15 cell line (which contains integrated HBV genome) and its parent cell line HepG2. Among 38,500 genes analyzed, expression of 1305 genes changed more than 2 fold in HepG2.2.15. we found that heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3 B1 (HS3ST3B1,3-OST3-B), a member of Heparan sulfate 3-O-sulfotransferase (3-OST), was significantly down regulated in HepG2.2.15 line. HS3ST3B1 shows potent inhibitory effect on HBV replication in both transcient transfection model and cell model which support HBV replication stably. HBV replication can be restored when HS3ST3B1 expression was silenced by shRNA or loss-of-function HS3ST3B1 mutants were used. In apart from inhibiting HBV replication, viral protein as well as total RNA expression is suppressed when HS3ST3B1 over expressed.This study demonstrated that HS3ST3B1 may function as potential HBV inhibitor. Future studies should be devoted to understanding the exact mechanism on HS3ST3B1 on HBV replication, and exploring HS3ST3B1 as a potential anti-HBV therapeutic target.