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Open Access Highly Accessed Research

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

Ruiping Ma1, Quantai Xing1, Lihua Shao2, Dakun Wang3, Qingzhi Hao4, Xia Li5, Lintao Sai1 and Lixian Ma1*

Author Affiliations

1 Department of Infectious Diseases, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China

2 Department of Laboratory Sciences, School of Public Health, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China

3 Cryo Medicine Laboratory, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China

4 Department of Peripheral Vascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Wenhua Xi Road 42, Jinan 250011, Shandong Province, China

5 Laboratory for Tumor Immunity and Traditional Chinese Drug Immunity, Institute of Basic Medicine, Shandong Academy of Medical Science, Jingshi Road 89, Jinan 250062 Shandong Province, China

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Virology Journal 2011, 8:486  doi:10.1186/1743-422X-8-486

Published: 31 October 2011

Abstract

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.

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.

Keywords:
Hepatitis B virus; Infection; Replication; Human bone marrow mesenchymal stem cell; Host Cell