Hepatitis B virus infection and replication in human bone marrow mesenchymal stem cells

BACKGROUND: Hepatitis B virus (HBV) infection is a blood borne infectious disease that affects the liver. Human bone marrow mesenchymal stem cells (BMSCs) may serve as a cell source for adult stem cell transplantation in liver repair. However, the susceptibility of human BMSCs to HBV infection is poorly understood. The aim of this study was to investigate the infection and replication of HBV in cultures of human BMSCs. RESULTS: Human BMSCs were confirmed using flow cytometry. Intracellular HBV DNA was detected at d 2 after infection and maintained at relatively high levels from d 6 to d 12. The maximal level of intracellular HBV DNA was 9.37 × 10(5 )copies/mL. The extracellular HBV DNA was observed from d 3 to d 15, and the levels ranged from 3.792 × 10(2 )copies/mL to 4.067 × 10(5 )copies/mL. HBsAg in the culture medium was detected from d 2 to d 16. HBeAg secretion was positive from d 5 to d 13. HBcAg constantly showed positive signals in approximately 7%-20% of BMSCs from 2 days after exposure. Intracellular HBV covalently closed circular DNA (cccDNA) could be detected as early as 2 days postinfection, and strong signals were obtained with increasing time. CONCLUSION: HBV can infect and replicate in human BMSCs. Human BMSCs may be a useful tool for investigating HBV life-cycle and the mechanism of initial virus-cell interactions.