title: In vitro hepatitis B virus infection of human bone marrow cells.
abstract: Infection of humans with hepatitis B virus (HBV) frequently results in suppression of hematopoiesis; in some cases this may lead to severe bone marrow failure. The mechanism whereby HBV infection affects hematopoiesis is unknown. In vitro exposure of human bone marrow to HBV results in a dose-dependent inhibition of erythroid (erythroid burst forming units, BFU-E; erythroid colony-forming units CFU-E), myeloid (colony-forming units-granulocyte macrophage CFU-GM), and lymphoid (CFU-[T-lymphocytic]-TL) hematopoietic stem cells. Inactivation or immunoabsorption of HBV from sera resulted in loss of HBV-induced inhibition of hematopoietic stem cells. De novo gamma interferon was not detectable in the supernatants of cultures of bone marrow cells with HBV. Antibodies to gamma interferon did not affect the suppression of hematopoietic stem cells by HBV. Hepatitis B surface antigen (HBsAg) was detected by immune electron microscopy in nuclei of greater than 70% of immature hematopoietic cells including myeloblasts, normoblasts, and lymphoblasts; granulocytes had mostly cytoplasmic HBsAg. Hepatitis B virus core antigen (HBcAg) was also detected in about 5% of HBV infected bone marrow cells by immunoperoxidase staining. These data indicate that HBV can infect hematopoietic cells and their progenitors, thus suggesting a wider range of tropism for HBV than previously reported. These results may provide a basis to study HBV infection in vitro, and the effects of HBV on hematopoiesis.
mesh_terms: D000961:Antilymphocyte Serum / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology* / Q000648:ultrastructure; D002472:Cell Transformation, Viral; D003114:Colony-Forming Units Assay; D004279:DNA, Viral / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D006509:Hepatitis B / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology
chemical_list: D000961:Antilymphocyte Serum; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma