HEPATITIS-B VIRUS DIFFERENTIALLY SUPPRESSES MYELOPOIESIS AND DISPLAYSTROPISM FOR IMMATURE HEMATOPOIETIC-CELLS

The hematopoietic cell lines HL-60 and THP-1 were challenged with hepa titis B virus (HBV) in vitro to study interactions between the virus a nd host cell. Exposure to HBV suppressed the ability of HL-60 cells to differentiate into granulocytes after treatment with retinoic acid (R A) or dimethyl sulfoxide (DMSO), and RA-induced activation of the mono cytic cell line THP-1 was also suppressed. Terminal differentiation of both cell lines by phorbol 12-myristate 13-acetate (PMA) was not affe cted by HBV. The suppressive effect on RA- or DMSO-induced differentia tion was unique to HBV, since cell exposure to human cytomegalovirus, another virus that inhibits hematopoiesis, failed to block cellular di fferentiation. At 5 days postinfection, extracellular viral DNA was de tected in immature but not in differentiated cultures and higher level s of core antigen (HBcAg) and surface antigen (HBsAg) were seen in und ifferentiated cells than in RA- or PMA-treated cells. In addition, rel ease of HBsAg into the medium was 2 to 12 times greater in untreated c ultures than for RA- or PMA-treated cells. Thus, HBV suppresses hemato poiesis by blocking the maturational development of progenitors and se lectively infects immature myeloid cells compared with mature end-stag e cells.