Macrophage-derived exosomes inhibit HBV DNA replication

YANG Fan; YANG Tao; ZHOU Wen-jing; XU Ruo-nan; WANG Fu-sheng

doi:10.3969/j.issn.1007-8134.2018.02.008

Abstract：Objective To investigate the mechanism of macrophage-derived exosomes on inhibiting HBV replication and analyze its relationship with liver damage in chronic hepatitis B (CHB) patients. Methods Macrophage-derived exosomes were isolated in vitro and co-cultured with HepG2.2.15 cells. Real-time quantitive PCR was used to detect the change of HBV DNA replication after co-culture, and the expression levels of microRNA-638 (miRNA-638) in the exosomes isolated from macrophages and supernatant were analyzed. In addition, CHB patients at immune activation (IA) and inactive carrier (IC) stage, as well as healthy controls were included in this study. The miRNA-638 expression level in macrophage-derived exosomes was detected with real-time quantitive PCR, and its correlation with liver damage and HBV DNA load was analyzed. Results Exosomes derived from macrophages could inhibit HBV DNA replication, and miRNA-638 expression upregulated in the exosomes isolated from macrophages and supernatant; miRNA-638 expression decreased in the CHB patients at IA stage compared with that at IC stage; miRNA-638 expression was negatively correlated with ALT, AST, and HBV DNA in the serum exosomes of CHB patients. Conclusions Exosomes derived from macrophage may inhibit HBV DNA replication. miRNA-638 expression in exosomes is closely associated with liver inflammation injury and viral replication. Exosomes associated miRNA in macrophages may be a potential target for inhibiting HBV replication and reducing liver inflammation.