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 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.
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- Blum H. E., Stowring L., Figus A., Montgomery C. K., Haase A. T., Vyas G. N. Detection of hepatitis B virus DNA in hepatocytes, bile duct epithelium, and vascular elements by in situ hybridization. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6685–6688. doi: 10.1073/pnas.80.21.6685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bouffard P., Lamelin J. P., Zoulim F., Pichoud C., Trepo C. Different forms of hepatitis B virus DNA and expression of HBV antigens in peripheral blood mononuclear cells in chronic hepatitis B. J Med Virol. 1990 Aug;31(4):312–317. doi: 10.1002/jmv.1890310413. [DOI] [PubMed] [Google Scholar]
- Broxmeyer H. E., Lu L., Platzer E., Feit C., Juliano L., Rubin B. Y. Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J Immunol. 1983 Sep;131(3):1300–1305. [PubMed] [Google Scholar]
- Busch F. W., de Vos S., Flehmig B., Herrmann F., Sandler C., Vallbracht A. Inhibition of in vitro hematopoiesis by hepatitis A virus. Exp Hematol. 1987 Oct;15(9):978–982. [PubMed] [Google Scholar]
- Chang H. K., Ting L. P. The surface gene promoter of the human hepatitis B virus displays a preference for differentiated hepatocytes. Virology. 1989 May;170(1):176–183. doi: 10.1016/0042-6822(89)90364-4. [DOI] [PubMed] [Google Scholar]
- Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins S. J. The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood. 1987 Nov;70(5):1233–1244. [PubMed] [Google Scholar]
- Dejean A., Lugassy C., Zafrani S., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. J Gen Virol. 1984 Mar;65(Pt 3):651–655. doi: 10.1099/0022-1317-65-3-651. [DOI] [PubMed] [Google Scholar]
- Donahue R. E., Johnson M. M., Zon L. I., Clark S. C., Groopman J. E. Suppression of in vitro haematopoiesis following human immunodeficiency virus infection. Nature. 1987 Mar 12;326(6109):200–203. doi: 10.1038/326200a0. [DOI] [PubMed] [Google Scholar]
- Gerber M. A., Sells M. A., Chen M. L., Thung S. N., Tabibzadeh S. S., Hood A., Acs G. Morphologic, immunohistochemical, and ultrastructural studies of the production of hepatitis B virus in vitro. Lab Invest. 1988 Aug;59(2):173–180. [PubMed] [Google Scholar]
- Harrison T. J. Hepatitis B virus DNA in peripheral blood leukocytes: a brief review. J Med Virol. 1990 May;31(1):33–35. doi: 10.1002/jmv.1890310107. [DOI] [PubMed] [Google Scholar]
- Lee J., Mehta K., Blick M. B., Gutterman J. U., Lopez-Berestein G. Expression of c-fos, c-myb, and c-myc in human monocytes: correlation with monocytic differentiation. Blood. 1987 May;69(5):1542–1545. [PubMed] [Google Scholar]
- Lie-Injo L. E., Balasegaram M., Lopez C. G., Herrera A. R. Hepatitis B virus DNA in liver and white blood cells of patients with hepatoma. DNA. 1983;2(4):301–308. doi: 10.1089/dna.1983.2.301. [DOI] [PubMed] [Google Scholar]
- Lobbiani A., Lalatta F., Lugo F., Colucci G. Hepatitis B virus transcripts and surface antigen in human peripheral blood lymphocytes. J Med Virol. 1990 Jul;31(3):190–194. doi: 10.1002/jmv.1890310304. [DOI] [PubMed] [Google Scholar]
- Mehta K., Lopez-Berestein G. Expression of tissue transglutaminase in cultured monocytic leukemia (THP-1) cells during differentiation. Cancer Res. 1986 Mar;46(3):1388–1394. [PubMed] [Google Scholar]
- Munker R., Koeffler P. In vitro action of tumor necrosis factor on myeloid leukemia cells. Blood. 1987 Apr;69(4):1102–1108. [PubMed] [Google Scholar]
- Müller C., Bergmann K. F., Gerin J. L., Korba B. E. Production of hepatitis B virus by stably transfected monocytic cell line U-937: a model for extrahepatic hepatitis B virus replication. J Infect Dis. 1992 May;165(5):929–933. doi: 10.1093/infdis/165.5.929. [DOI] [PubMed] [Google Scholar]
- Neurath A. R., Strick N., Sproul P., Ralph H. E., Valinsky J. Detection of receptors for hepatitis B virus on cells of extrahepatic origin. Virology. 1990 Jun;176(2):448–457. doi: 10.1016/0042-6822(90)90014-i. [DOI] [PubMed] [Google Scholar]
- Raney A. K., Milich D. R., Easton A. J., McLachlan A. Differentiation-specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. J Virol. 1990 May;64(5):2360–2368. doi: 10.1128/jvi.64.5.2360-2368.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roingeard P., Lu S. L., Sureau C., Freschlin M., Arbeille B., Essex M., Romet-Lemonne J. L. Immunocytochemical and electron microscopic study of hepatitis B virus antigen and complete particle production in hepatitis B virus DNA transfected HepG2 cells. Hepatology. 1990 Feb;11(2):277–285. doi: 10.1002/hep.1840110219. [DOI] [PubMed] [Google Scholar]
- Scott J. S., Pace R. A., Sheridan J. W., Cooksley W. G. Discordance of hepatitis B e antigen and hepatitis B viral deoxyribonucleic acid. J Med Virol. 1990 Dec;32(4):225–231. doi: 10.1002/jmv.1890320406. [DOI] [PubMed] [Google Scholar]
- Sing G. K., Keller J. R., Ellingsworth L. R., Ruscetti F. W. Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro. Blood. 1988 Nov;72(5):1504–1511. [PubMed] [Google Scholar]
- Sing G. K., Ruscetti F. W. Preferential suppression of myelopoiesis in normal human bone marrow cells after in vitro challenge with human cytomegalovirus. Blood. 1990 May 15;75(10):1965–1973. [PubMed] [Google Scholar]
- Steinberg H. S., Bouffard P., Trépo C., Zeldis J. B. In vitro inhibition of hemopoietic cell line growth by hepatitis B virus. J Virol. 1990 Jun;64(6):2577–2581. doi: 10.1128/jvi.64.6.2577-2581.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsuchiya S., Yamabe M., Yamaguchi Y., Kobayashi Y., Konno T., Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980 Aug;26(2):171–176. doi: 10.1002/ijc.2910260208. [DOI] [PubMed] [Google Scholar]
- Zeldis J. B., Boender P. J., Hellings J. A., Steinberg H. Inhibition of human hemopoiesis by non-A, non-B hepatitis virus. J Med Virol. 1989 Jan;27(1):34–38. doi: 10.1002/jmv.1890270108. [DOI] [PubMed] [Google Scholar]
- Zeldis J. B., Mugishima H., Steinberg H. N., Nir E., Gale R. P. In vitro hepatitis B virus infection of human bone marrow cells. J Clin Invest. 1986 Aug;78(2):411–417. doi: 10.1172/JCI112591. [DOI] [PMC free article] [PubMed] [Google Scholar]