The hematopoietic cell lines HL-60 and THP-1 were challenged with hepatitis B virus (HBV) in vitro to study interactions between the virus and host cell. Exposure to HBV suppressed the ability of HL-60 cells to differentiate into granulocytes after treatment with retinoic acid (RA) or dimethyl sulfoxide (DMSO), and RA-induced activation of the monocytic cell line THP-1 was also suppressed. Terminal differentiation of both cell lines by phorbol 12-myristate 13-acetate (PMA) was not affected by HBV. The suppressive effect on RAor DMSO-induced differentiation was unique to HBV, since cell exposure to human cytomegalovirus, another virus that inhibits hematopoiesis, failed to block cellular differentiation. At 5 days postinfection, extracellular viral DNA was detected in immature but not in differentiated cultures and higher levels of core antigen (HBcAg) and surface antigen (HBsAg) were seen in undifferentiated cells than in RAor PMA-treated cells. In addition, release of HBsAg into the medium was 2 to 12 times greater in untreated cultures than for RAor PMA-treated cells. Thus, HBV suppresses hematopoiesis by blocking the maturational development of progenitors and selectively infects immature myeloid cells compared with mature end-stage cells.
Suspension cultures of bone marrow cells (BMC) were challenged with hepatitis B virus (HBV) to study interactions between the virus and the nonadherent and adherent BMC populations. Virus-challenged BMC developed an adherent stromal layer that differed in cellular composition from that of mock-infected cultures, showing a threefold increase in cells of the monocyte-macrophage lineage with an accompanying decrease in cells of the granulocytic lineage. Both viral envelope hepatitis B surface and core antigen expression was detected in adherent and nonadherent cell populations up to 10 days after virus challenge, which decreased thereafter. HBV DNA was still detectable in adherent cells 3 weeks after virus challenge, as shown by polymerase chain reaction analysis. These data indicate that HBV can infect not only bone marrow colony-forming cells but also the stromal cell populations involved with the regulation of hematopoiesis in vivo. Such virus-cell interactions could contribute to the immune dysfunction and bone marrow failure occasionally reported for patients with HBV infection as well as acting as an important site for HBV latency and persistence.
We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF‐1, was established from a hepatocellular carcinoma of a 67‐yr‐old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI‐1640 tissue‐culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, α2‐macroglobulin, fibronectin and α‐fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF‐1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload. (Hepatology 1994;20:74–81.)
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