Abstract
Infection of humans with hepatitis B virus (HBV) frequently results in suppression of hematopoiesis; in some cases this may lead to severe bone marrow failure. The mechanism whereby HBV infection affects hematopoiesis is unknown. In vitro exposure of human bone marrow to HBV results in a dose-dependent inhibition of erythroid (erythroid burst forming units, BFU-E; erythroid colony-forming units CFU-E), myeloid (colony-forming units-granulocyte macrophage CFU-GM), and lymphoid (CFU-[T-lymphocytic]-TL) hematopoietic stem cells. Inactivation or immunoabsorption of HBV from sera resulted in loss of HBV-induced inhibition of hematopoietic stem cells. De novo gamma interferon was not detectable in the supernatants of cultures of bone marrow cells with HBV. Antibodies to gamma interferon did not affect the suppression of hematopoietic stem cells by HBV. Hepatitis B surface antigen (HBsAg) was detected by immune electron microscopy in nuclei of greater than 70% of immature hematopoietic cells including myeloblasts, normoblasts, and lymphoblasts; granulocytes had mostly cytoplasmic HBsAg. Hepatitis B virus core antigen (HBcAg) was also detected in about 5% of HBV infected bone marrow cells by immunoperoxidase staining. These data indicate that HBV can infect hematopoietic cells and their progenitors, thus suggesting a wider range of tropism for HBV than previously reported. These results may provide a basis to study HBV infection in vitro, and the effects of HBV on hematopoiesis.
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- Blum H. E., Haase A. T., Vyas G. N. Molecular pathogenesis of hepatitis B virus infection: simultaneous detection of viral DNA and antigens in paraffin-embedded liver sections. Lancet. 1984 Oct 6;2(8406):771–775. doi: 10.1016/s0140-6736(84)90703-7. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Djeu J. Y., Stocks N., Zoon K., Stanton G. J., Timonen T., Herberman R. B. Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses. J Exp Med. 1982 Oct 1;156(4):1222–1234. doi: 10.1084/jem.156.4.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
- Kermani-Arab V., Hirji K., Ahmed A. R., Fahey J. L. Deficiency of interleukin-2 production and interleukin-2 receptor expression on peripheral blood leukocytes after phytohemagglutinin stimulation in pemphigus. J Invest Dermatol. 1984 Aug;83(2):101–104. doi: 10.1111/1523-1747.ep12263194. [DOI] [PubMed] [Google Scholar]
- Laure F., Zagury D., Saimot A. G., Gallo R. C., Hahn B. H., Brechot C. Hepatitis B virus DNA sequences in lymphoid cells from patients with AIDS and AIDS-related complex. Science. 1985 Aug 9;229(4713):561–563. doi: 10.1126/science.2410981. [DOI] [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]
- Pontisso P., Poon M. C., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in mononuclear blood cells. Br Med J (Clin Res Ed) 1984 May 26;288(6430):1563–1566. doi: 10.1136/bmj.288.6430.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigby W. F., Ball E. D., Guyre P. M., Fanger M. W. The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells. Blood. 1985 Apr;65(4):858–861. [PubMed] [Google Scholar]
- Romet-Lemonne J. L., McLane M. F., Elfassi E., Haseltine W. A., Azocar J., Essex M. Hepatitis B virus infection in cultured human lymphoblastoid cells. Science. 1983 Aug 12;221(4611):667–669. doi: 10.1126/science.6867736. [DOI] [PubMed] [Google Scholar]
- Scotto J., Hadchouel M., Hery C., Yvart J., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in serum by a simple spot hybridization technique: comparison with results for other viral markers. Hepatology. 1983 May-Jun;3(3):279–284. doi: 10.1002/hep.1840030301. [DOI] [PubMed] [Google Scholar]
- Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
- Toretsky J. A., Shahidi N. T., Finlay J. L. Effects of recombinant human interferon gamma on hematopoietic progenitor cell growth. Exp Hematol. 1986 Mar;14(3):182–186. [PubMed] [Google Scholar]
- Young N. S., Mortimer P. P., Moore J. G., Humphries R. K. Characterization of a virus that causes transient aplastic crisis. J Clin Invest. 1984 Jan;73(1):224–230. doi: 10.1172/JCI111195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeldis J. B., Dienstag J. L., Gale R. P. Aplastic anemia and non-A, non-B hepatitis. Am J Med. 1983 Jan;74(1):64–68. doi: 10.1016/0002-9343(83)91119-1. [DOI] [PubMed] [Google Scholar]
- Zoumbos N. C., Djeu J. Y., Young N. S. Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro. J Immunol. 1984 Aug;133(2):769–774. [PubMed] [Google Scholar]
- Zoumbos N. C., Gascon P., Djeu J. Y., Young N. S. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc Natl Acad Sci U S A. 1985 Jan;82(1):188–192. doi: 10.1073/pnas.82.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]