Hepatitis B virus differentially suppresses myelopoiesis and displays tropism for immature hematopoietic cells

Abstract

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.

Bone marrow‐derived mesenchymal stem cells are capable of mediating hepatitis B virus infection in injured tissues

“…Although a number of studies have demonstrated that HBV DNA or HBV antigen was detected in PBMCs [25] or BM cells MSCs are capable of mediating HBV infection 611 [12,26,27] suggesting that these cells can be infected with HBV, some others have also reported that the HBV is not replicated in PBMCs [13]. The evidence for replication of HBV at extrahepatic sites remains controversial.…”

“…Several studies have demonstrated that HBV replication occurred in a variety of extrahepatic tissues and cell types, which has been also proposed to be involved in the pathogenesis of extrahepatic disease [5][6][7][8][9][10][11][12]. Recent studies revealed that many different cell types such as endothelial cells, epithelial cells, neurons, macrophages, bone marrow cells, peripheral blood mononuclear cells and polymorph nuclear leukocytes are permissive for HBV replication [4,8,[10][11][12]. However, in contrast, several other studies have demonstrated that the HBV is not replicated in peripheral blood mononuclear cells (PBMCs) [13], endothelial cells [14] and lymphatic tissues [15].…”

Erythrocytosis after liver transplantation: The experience of a university hospital

“…The bone marrow has been termed a sanctuary for HBV, and it displays tropism for immature hematopoietic cells. 10,11 HCV also shows tropism for bone marrow cells but with a different spectrum of findings. 12 An HCV infection has no evident directly suppressive effect on bone marrow, whereas an HBV infection frequently results in the suppression of hematopoiesis.…”

Possible Involvement of Hepatitis B Virus Infection of Hepatocytes in the Attenuation of Apoptosis in Hepatic Stellate Cells

“…Conditioned media were prepared similarly from PXB cells at 17 days after infection with or without HBV [ 24 ]. Ultraviolet (UV)-inactivated virus was prepared by irradiating conditioned media samples with a UV trans-illuminator as previously described [ 26 ].…”