1887

Journal of General Virology header logo

Volume 67, Issue 12

Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells Free

Abstract

Summary

As an attempt to elucidate further the pathogenesis of human cytomegalovirus (HCMV) infection the replication of HCMV in primary human bone marrow cells (BMC) has been investigated. It was found that BMC held in culture in general were susceptible to HCMV infection. Compared to human embryonic lung cells, however, the replicative cycle of HCMV AD169 in BMC as determined by the analysis of viral protein and DNA synthesis was delayed and productive virus infection was restricted to a subset of BMC not exceeding 21% of the total cell population. Both of these phenomena may explain the short-term persistence of HCMV in BMC cultures which was observed over 3 months. By experiments with specifically enriched and depleted cell populations and by indirect double immunofluorescence experiments we found that both bone marrow fibroblasts and a subset of bone marrow stem cells supported productive virus infection. The finding that HCMV replicates in early stem cells of the human bone marrow may explain important aspects of the pathogenesis of HCMV infection including the presence of HCMV in peripheral blood leukocytes.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): HCMV , human bone marrow cells and replication
© Journal of General Virology 1986
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-67-12-2595
1986-12-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/67/12/JV0670122595.html?itemId=/content/journal/jgv/10.1099/0022-1317-67-12-2595&mimeType=html&fmt=ahah

References

  1. Bodem C. R., Hamory N. H., Taylor H. M., Kleopfer L. 1983; Granulomatous bone marrow disease. Medicine, Baltimore 62:372–383
     [Google Scholar]
  2. Brandsma J., Miller G. 1980; Nucleic acid spot hybridization: rapid quantitative screening of lymphoid cell lines for Epstein-Barr viral DNA. Proceedings of the National Academy of Sciences, U.S.A. 77:6851–6855
     [Google Scholar]
  3. Braun R. W., Teute H. K., Kirchner H., Munk K. 1984; Replication of herpes simplex virus in human T lymphocytes: characterization of the viral target cell. Journal of Immunology 132:914–919
     [Google Scholar]
  4. Braun R. W., Reiser H. 1986; Replication of human cytomegalovirus in human peripheral blood T cells. Journal of Virology (in press)
    [Google Scholar]
  5. Brunning R. D. 1981; Bone marrow. In Ackerman’s Surgical Pathology pp 1251–1303 Edited by Rosai J. St. Louis, Toronto & London: C. V. Mosby;
     [Google Scholar]
  6. Carney W. P., Rubin R. H., Hoffmann R. A., Hansen W. P., Healek K., Hirsch M. S. 1981; Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis. Journal of Immunology 126:2114–2116
     [Google Scholar]
  7. Crawford D. H., Francis G. E., Wing M. A., Edwards A. J., Janossy G., Hoffbrand A. V., Prentice H. G., Secher D., Mcconnell I., Kung P. C., Goldstein G. 1981; Reactivity of monoclonal antibodies with human myeloid precursor cells. British Journal of Haematology 49:209–217
     [Google Scholar]
  8. Daniels C. A., Kleinermann E. S., Snyderman R. 1978; Abortive and productive infections of human mononuclear phagocytes by type 1 herpes simplex virus. American Journal of Pathology 91:119–136
     [Google Scholar]
  9. Demarchi J. M., Kaplan A. S. 1977; The role of defective cytomegalovirus particles in the induction of host cell DNA synthesis. Virology 82:93–99
     [Google Scholar]
  10. Einhorn L., Sst A. 1984; Cytomegalovirus infection of human blood cells. Journal of Infectious Diseases 149:207–214
     [Google Scholar]
  11. Farrar G. H., Oram J. D. 1984; Characterization of the human cytomegalovirus envelope glycoproteins. Journal of General Virology 65:1991–2001
     [Google Scholar]
  12. Fiala M., Payne J. E., Berne T. V., Moore J. C., Henle W., Montgomerie J. Z., Chaterjee S. N., Guze L. B. 1975; Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. Journal of Infectious Diseases 132:421–433
     [Google Scholar]
  13. Furukuwa T. 1979; Persistent infection with human cytomegalovirus in a lymphoblastoid cell line. Virology 94:214–218
     [Google Scholar]
  14. Gartner S., Kaplan H. S. 1980; Long-term culture of human bone marrow cells. Proceedings of the National Academy of Sciences, U.S.A. 77:4756–4759
     [Google Scholar]
  15. Gonczol E., Andrews P. W., Plotkin S. A. 1984; Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells. Science 224:159–161
     [Google Scholar]
  16. Greaves M. F. 1981; Monoclonal antibodies as probes for leukemic heterogeneity and haematopoietic differentiation. In Leukemia Markers pp 19–32 Edited by Knapp W. London: Academic Press;
     [Google Scholar]
  17. Harnden D. G., Elsdale T. R., Young D. E., Ross A. 1967; The isolation of cytomegalovirus from peripheral blood. Blood 30:120–125
     [Google Scholar]
  18. Hirsch M. S. 1984; Cytomegalovirus-leukocyte interactions. Birth Defects: Original Article Series 20:161–173
     [Google Scholar]
  19. Anossy G., Tidman N., Papageorgiou E. S., Rung P. C., Goldstein G. 1981; Distribution of T lymphocyte subsets in the human bone marrow and thymus - an analysis with monoclonal antibodies. Journal of Immunology 126:1608–1613
     [Google Scholar]
  20. Janossy S. H., Menezes J., Huang E.-S. 1975; Persistence of human cytomegalovirus in lymphoid cells after congenital infection. Nature, London 258:432–434
     [Google Scholar]
  21. Kirchner H. 1983; Immunobiology of infection with human cytomegalovirus. Advances in Cancer Research 40:31–105
     [Google Scholar]
  22. McDonough S. H., Spector D. H. 1983; Transcription in human fibroblasts permissively infected by human cytomegalovirus strain AD 169. Virology 125:31–46
     [Google Scholar]
  23. Macher A. M., Reichert C. M., Straus S. E., Longo D. L., Parillo J., Lane H. C., Fauci A. S., Eook A. H., Manischewitz J. F., & Quinnan G. V. Jr 1983; Death in the AIDS patient: role of cytomegalovirus. New England Journal of Medicine 309:1454
     [Google Scholar]
  24. Neimann P. E., Reeves W., Ray G., Flournoy N., Lerner K. G., Slae G. E., Thomas E. D. 1977; A prospective analysis of interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts. Journal of Infectious Diseases 136:754–767
     [Google Scholar]
  25. Nowak B., Sullivan C., Sirnow P., Thomas R., Bricout F., Nicolas J. C., Fleckenstein B., Levine A. J. 1984; Characterization of monoclonal antibody and polyclonal immune sera directed against human cytomegalovirus virion proteins. Virology 132:325–338
     [Google Scholar]
  26. Oakley B. R., Kirsch D. R., Morris N. R. 1980; A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Analytical Biochemistry 105:361–363
     [Google Scholar]
  27. Rapp F. 1984; Cytomegalovirus and carcinogenesis. Journal of the National Cancer Institute 72:783–787
     [Google Scholar]
  28. Rice G. P. A., Schrier R. D., Oldstone M. B. A. 1984; Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate early gene products. Proceedings of the National Academy of Sciences, U.S.A. 81:6134–6138
     [Google Scholar]
  29. Rinaldo C. R. JR, Black P. H., Hirsch M. S. 1977; Virus-leukocyte interactions in cytomegalovirus mononucleosis. Journal of Infectious Diseases 136:667–678
     [Google Scholar]
  30. Rinaldo C. R., Richter B. S., Black P. H., Callery R., Chess L., Jirsch M. S. 1978; Replication of herpes simplex virus and cytomegalovirus in human leukocytes. Journal of Immunology 120:130–136
     [Google Scholar]
  31. Rinaldo C. R. Jr, Carney W. P., Richter B. S., Black P. H., Hirsch M. S. 1980; Mechanisms of immunosuppression in cytomegalovirus mononucleosis. Journal of Infectious Diseases 141:488–495
     [Google Scholar]
  32. Ruger R., Bornkamm G. W., Fleckenstein B. 1984; Human cytomegalovirus DNA sequences with homologies to the cellular genome. Journal of General Virology 65:1351–1364
     [Google Scholar]
  33. Schober L., Braun R., Reiser H., Munk K., Leroux M., Kirchner H. 1984; Ia-positive T lymphocytes are the producer cells of interferon gamma. Experimental Cell Research 152:348–356
     [Google Scholar]
  34. Schrier R. D., Nelson J. A., Oldstone M. B. A. 1985; Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science 230:1048–1051
     [Google Scholar]
  35. Spector S. A., Rua J. A., Spector D. H., Mcmillan R. 1984; Detection of human cytomegalovirus in clinical specimens by DNA-DNA hybridization. Journal of Infectious Diseases 150:121–126
     [Google Scholar]
  36. Stinski M. F. 1977; Synthesis of proteins and glycoproteins in cells infected with human cytomegalovirus. Journal of Virology 23:751–767
     [Google Scholar]
  37. Stinski M. F., Thomsen D. R., Wathen M. W. 1981; Structure and function of the cytomegalovirus genome. In The Human Herpesviruses pp 72–84 Edited by Nahmias J. A., Dowdle W. R., Schinazi R. F. New York & Amsterdam:: North-Holland/Elsevier.;
     [Google Scholar]
  38. Switzer R. C. III, Merril C. R., Skifrin S. 1979; A highly sensitive silver stain for detecting proteins and peptides in polyacrylamide gels. Analytical Biochemistry 98:231–237
     [Google Scholar]
  39. Thomas J. O., Kornberg R. D. 1975; An octamer of histones in chromatin and free in solution. Proceedings of the National Academy of Sciences, U.S.A. 72:2626–2630
     [Google Scholar]
  40. Tumilowicz J. J., Gawlik M. E., Powell B. B., Trentin J. J. 1985; Replication of cytomegalovirus in human arterial smooth muscle cells. Journal of Virology 56:839–845
     [Google Scholar]
  41. Verdonck L. F., Van Heugten H., De Gast G. C. 1985; Delay in platelet recovery after bone marrow transplantation: impact of cytomegalovirus infection. Blood 66:921–925
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-67-12-2595
Loading
Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells
J. Gen. Virol. 67, 2595 (1986); https://doi.org/10.1099/0022-1317-67-12-2595
/content/journal/jgv/10.1099/0022-1317-67-12-2595
/content/journal/jgv/10.1099/0022-1317-67-12-2595
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error