title: Hepatitis B Virus Replication in CD34+ Hematopoietic Stem Cells From Umbilical Cord Blood.
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.
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Rongshan
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Shupeng
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Infectious Disease, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Disease, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Lan
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis*; D004279:DNA, Viral / Q000097:blood; D005312:Fetal Blood / Q000166:cytology / Q000821:virology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology*; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D014779:Virus Replication / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens