Virology Journal | |
Hepatitis B virus infection and replication in human bone marrow mesenchymal stem cells | |
Lixian Ma5  Lintao Sai5  Xia Li2  Qingzhi Hao1  Dakun Wang4  Lihua Shao3  Quantai Xing5  Ruiping Ma5  | |
[1] Department of Peripheral Vascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Wenhua Xi Road 42, Jinan 250011, Shandong Province, China;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;Department of Laboratory Sciences, School of Public Health, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China;Cryo Medicine Laboratory, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China;Department of Infectious Diseases, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China | |
关键词: Host Cell; Human bone marrow mesenchymal stem cell; Replication; Infection; Hepatitis B virus; | |
Others : 1155787 DOI : 10.1186/1743-422X-8-486 |
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received in 2011-09-18, accepted in 2011-10-31, 发布年份 2011 | |
【 摘 要 】
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.
【 授权许可】
2011 Ma et al; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 108KB | Image | download |
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【 参考文献 】
- [1]Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP: Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 2006, 28:112-125.
- [2]Gripon P, Diot C, Theze N, Fourel I, Loreal O, Brechot C, Guguen-Guillouzo C: Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J Virol 1988, 62:4136-4143.
- [3]Gripon P, Diot C, Guguen-Guillouzo C: Reproducible high level infection of cultured adult human hepatocytes by hepatitis B virus: effect of polyethylene glycol on adsorption and penetration. Virology 1993, 192:534-540.
- [4]Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK: In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004, 40:1275-1284.
- [5]Ishii K, Yoshida Y, Akechi Y, Sakabe T, Nishio R, Ikeda R, Terabayashi K, Matsumi Y, Gonda K, Okamoto H, et al.: Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3beta. Hepatology 2008, 48:597-606.
- [6]Aurich I, Mueller LP, Aurich H, Luetzkendorf J, Tisljar K, Dollinger MM, Schormann W, Walldorf J, Hengstler JG, Fleig WE, Christ B: Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 2007, 56:405-415.
- [7]Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW, Lee OK: Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 2008, 134:2111-2121. 2121 e2111-2113
- [8]Klintschar M, Neuhuber F: Evaluation of an alkaline lysis method for the extraction of DNA from whole blood and forensic stains for STR analysis. J Forensic Sci 2000, 45:669-673.
- [9]Summers J, Smith PM, Horwich AL: Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J Virol 1990, 64:2819-2824.
- [10]Yang W, Mason WS, Summers J: Covalently closed circular viral DNA formed from two types of linear DNA in woodchuck hepatitis virus-infected liver. J Virol 1996, 70:4567-4575.
- [11]Lu C, Li XY, Hu Y, Rowe RG, Weiss SJ: MT1-MMP controls human mesenchymal stem cell trafficking and differentiation. Blood 2010, 115:221-229.
- [12]Fellig Y, Almogy G, Galun E, Ketzinel-Gilad M: A hepatocellular carcinoma cell line producing mature hepatitis B viral particles. Biochem Biophys Res Commun 2004, 321:269-274.
- [13]Chin R, Nachbur U, Earnest-Silveira L, Bankovacki A, Koeberlein B, Zentgraf H, Bock CT, Silke J, Torresi J: Dysregulation of hepatocyte cell cycle and cell viability by hepatitis B virus. Virus Res 2010, 147:7-16.
- [14]Bae KS, Park JB, Kim HS, Kim DS, Park DJ, Kang SJ: Neuron-like differentiation of bone marrow-derived mesenchymal stem cells. Yonsei Med J 2011, 52:401-412.
- [15]Liu J, Yang Y, Hu B, Ma ZY, Huang HP, Yu Y, Liu SP, Lu MJ, Yang DL: Development of HBsAg-binding aptamers that bind HepG2.2.15 cells via HBV surface antigen. Virol Sin 2010, 25:27-35.
- [16]Lin M, Chen Q, Yang LY, Li WY, Cao XB, Wu JR, Peng YP, Chen MR: Hepatitis B virus infection and replication in primarily cultured human fetal hepatocytes. World J Gastroenterol 2007, 13:1027-1031.
- [17]Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, Guguen-Guillouzo C: Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci USA 2002, 99:15655-15660.
- [18]Tuttleman JS, Pourcel C, Summers J: Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 1986, 47:451-460.
- [19]Mason A, Wick M, White H, Perrillo R: Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection. Hepatology 1993, 18:781-789.