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 × 105 copies/mL. The extracellular HBV DNA was observed from d 3 to d 15, and the levels ranged from 3.792 × 102 copies/mL to 4.067 × 105 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.


CONCLUSIONS
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.
Department of Infectious Diseases, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China.
Ruiping
R
Ma
Quantai
Q
Xing
Lihua
L
Shao
Dakun
D
Wang
Qingzhi
Q
Hao
Xia
X
Li
Lintao
L
Sai
Lixian
L
Ma
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000821:virology*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000254:growth & development*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000821:virology*; D055815:Young Adult
D003470:Culture Media; D004279:DNA, Viral; D006513:Hepatitis B e Antigens