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

Yanxin Huang, Qin Yan, Rongshan Fan, Shupeng Song, Hong Ren, Yongguo Li, Yinghua Lan

(Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland))

Med Sci Monit 2016; 22:1673-1681

DOI: 10.12659/MSM.898680

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.

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