Hepatitis B virus differentially suppresses myelopoiesis and displays tropism for immature hematopoietic cells.
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 RA- or 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 RA- or PMA-treated cells. In addition, release of HBsAg into the medium was 2 to 12 times greater in untreated cultures than for RA- or 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.
Clinical Research Centre, Royal Brisbane Hospital Foundation, Bancroft Centre, Herston, Queensland, Australia.
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Cooksley
D001853:Bone Marrow / Q000254:growth & development / Q000382:microbiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004279:DNA, Viral / Q000032:analysis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004950:Esterases / Q000032:analysis; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000382:microbiology*; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000254:growth & development*; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D013778:Tetrazolium Salts; C011314:neotetrazolium; D014212:Tretinoin; D004950:Esterases; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide