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18 May 2016 : Hypothesis  

Hepatitis B Virus Replication in CD34+ Hematopoietic Stem Cells From Umbilical Cord Blood

Yanxin HuangBCDEF, Qin YanBDE, Rongshan FanBD, Shupeng SongBDF, Hong RenAG, Yongguo LiAEG, Yinghua LanACDE

DOI: 10.12659/MSM.898680

Med Sci Monit 2016; 22:1673-1681

Abstract

BACKGROUND
Hepatitis B virus (HBV) is a hepatotropic virus that can infect extrahepatic tissue. Whether hematopoietic stem cells (HSCs) can be infected by HBV and serve as a potential virus reservoir is still unknown. In this study, the susceptibility of CD34+ HSCs to HBV was investigated.
MATERIAL AND METHODS
Cord blood–derived CD34+ HSCs were exposed to HBV in vitro, and immunocytochemistry, transmission electron microscopy, and RT-PCR were used to identify viral-related proteins and specific viral genomic sequences. Then, CD34+ HSCs were challenged by different titers of HBV, and intracellular and supernatant HBV DNA, and hepatitis B surface antigen (HBsAg) levels, were examined. In addition, CD34+ peripheral blood stem cells (PBSCs) from chronic HBV carriers were isolated and cultured, and HBV DNA levels were measured.
RESULTS
HBV-infected CD34+ cells showed positive signals for HBsAg by DAB staining and TRITC staining, and HBV particles were identified. RT-PCR results showed that the 403 bp PCR products corresponding to the amplified hepatitis B S gene fragment were observed in CD34+ HSCs infected by HBV. In addition, supernatant and intracellular HBV DNA increased with the proliferation of CD34+ HSCs. Similar results were obtained from intracellular HBsAg quantification tests. In addition, HBV DNA levels both in cells and in supernatants of CD34+ PBSCs increased proportionally, and the increments of HBV DNA in the supernatants paralleled those found in cells.
CONCLUSIONS
HBV can replicate in CD34+ HSCs in cord blood or peripheral blood of chronic HBV carriers.

Keywords: Antigens, CD34 - biosynthesis, DNA, Viral - blood, Fetal Blood - virology, Hematopoietic Stem Cells - virology, Hepatitis B Surface Antigens - blood, Hepatitis B virus - physiology, Virus Replication - physiology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750