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

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/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.