1887

Abstract

High titre replication of human cytomegalovirus (HCMV) in cell culture is restricted to primary human fibroblasts. During acute infection , HCMV nucleic acids and antigens have been found in various organs. Using only morphological criteria, inconsistent data have been reported about the cell types that can be infected by HCMV. In particular, the role of fibroblasts in organ infections has remained unclear. To define accurately the target cells of HCMV , tissue sections from lung and gastrointestinal tract of patients suffering from acute HCMV infection were investigated using immunohistochemical double-labelling analyses. Monoclonal antibodies with defined specificity against immediate early (IE), early (E) and late (L) viral antigens and antibodies directed against cell marker proteins were employed to identify infected cells. The results demonstrated that a broad spectrum of cells was infected by HCMV . Consistent with their susceptibility in culture, fibroblasts formed a major population of HCMV-infected cells. In contrast, haemopoietic cells were only infrequently stained with virus-specific antibodies. Fibroblasts, epithelial cells, endothelial cells, smooth muscle cells and macrophages appeared to be permissive for HCMV replication. Contrary to this, polymorphonuclear cells showed only IE gene expression, indicating that these cells were abortively infected. The analysis of the distribution of infected cells in tissue supported the hypothesis that endothelial cells and monocytes/macrophages may play a crucial role in the haematogenous spread of HCMV; in contrast, fibroblasts, smooth muscle cells and epithelial cells may form the cell populations important for the multiplication and spread of the virus in infected tissues.

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1995-04-01
2024-12-10
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References

  1. Alford C. A., Britt W. J. 1990; Cytomegalovirus. In Virology 2nd edn pp 1981–2010 Edited by Fields B. N., Knipe D. M. New York: Raven Press;
    [Google Scholar]
  2. Alford C. A., Stagno S., Pass R. F., Britt W. J. 1990; Congenital and perinatal cytomegalovirus infections. Reviews of Infectious Diseases 12:S745–S753
    [Google Scholar]
  3. Aqel N. M., Tanner P., Drury A., Francis N. D., Henry K. 1991; Cytomegalovirus gastritis with perforation and gastrocolic fistula formation. Histopathology 18:165–168
    [Google Scholar]
  4. Aukrust P., Farstad I. N., Froland S. S., Holter E. 1992; Cytomegalovirus (CMV) pneumonitis in AIDS patients: the result of intensive CMV replication?. European Respiratory Journal 5:362–364
    [Google Scholar]
  5. Balthesen M., Messerle M., Reddehase M. J. 1993; Lungs are a major organ site of cytomegalovirus latency and recurrence. Journal of Virology 67:5360–5366
    [Google Scholar]
  6. Clarke L. M., Daidone B. J., Inghida R., Kirwin M., Sierra M. F. 1992; Differential recovery of cytomegalovirus from cellular and supernatant components of bronchoalveolar lavage specimens. American Journal of Clinical Pathology 97:313–317
    [Google Scholar]
  7. Cordonnier C., Escudier E., Nicolas J. C., Fleury J., Deforges L., Ingrand D., Bricout F., Bernaudin J. F. 1987; Evaluation of three assays on alveolar lavage fluid in the diagnosis of cytomegalovirus pneumonitis after bone marrow transplantation. Journal of Infectious Diseases 155:495–500
    [Google Scholar]
  8. Duncan A. J., Dummer J. S., Paradis I. L., Dauber J. H., Yousem S. A., Zenati M. A., Kormos R. L., Griffith B. P. 1991; Cytomegalovirus infection and survival in lung transplant recipients. Journal of Heart and Lung Transplantation 10:638–644
    [Google Scholar]
  9. Francis N. D., Boylston A. W., Roberts A. H., Parkin J. M., Pinching A. J. 1989; Cytomegalovirus infection in gastrointestinal tracts of patients infected with HIV-1 or AIDS. Journal of Clinical Pathology 42:1055–1064
    [Google Scholar]
  10. Gerna G., Revello M. G., Percivalle E., Morini F. 1992a; Comparison of different immunostaining techniques and monoclonal antibodies to the lower matrix phosphoprotein (pp65) for optimal quantification of human cytomegalovirus antigenemia. Journal of Clinical Microbiology 30:1232–1237
    [Google Scholar]
  11. Gerna G., Zipeto D., Percivalle E., Parea M., Revello M. G., Maccario R., Peri G., Milanesi G. 1992b; Human cytomegalovirus infection of the major leukocyte subpopulations and evidence for initial viral replication in polymorphonuclear leukocytes from viremic patients. Journal of Infectious Diseases 166:1236–1244
    [Google Scholar]
  12. Gibson W. 1993; Molecular biology of human cytomegalovirus. In Molecular aspects of human cytomegalovirus disease pp 303–329 Edited by Becker Y., Darai G., Huang E. S. Berlin: Springer;
    [Google Scholar]
  13. Gnann J. W. J., Ahlmen J., Svalander C., Olding L., Oldstone M. B., Nelson J. A. 1988; Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus. American Journal of Pathology 132:239–248
    [Google Scholar]
  14. Grefte J. M., Van der Gun B. T. F., Schmolke S., Van der Giessen M., Van Son W. J., Plachter B., Jahn G., The T. H. 1991; The lower matrix protein pp65 is the principal viral antigen present in peripheral blood leukocytes during an active cytomegalovirus infection. Journal of General Virology 73:2923–2932
    [Google Scholar]
  15. Grefte A., Van der Giessen M., Van Son W., The T. H. 1993a; Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. Journal of Infectious Diseases 167:270–277
    [Google Scholar]
  16. Grefte A., Blom N., Van der Giessen M., Van Son W., The T. H. 1993b; Ultrastructural analysis of circulating cytomegalic cells in patients with active cytomegalovirus infection: evidence for virus production and endothelial origin. Journal of Infectious Diseases 168:1110–1118
    [Google Scholar]
  17. Ibanez C. E., Schrier R., Ghazal P., Wiley C., Nelson J. A. 1991; Human cytomegalovirus productively infects primary differentiated macrophages. Journal of Virology 65:6581–6588
    [Google Scholar]
  18. Jacobson M. A., Mills J. 1988; Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Annals of Internal Medicine 108:585–594
    [Google Scholar]
  19. Jahn G., Harthus H. P., Broker M., Borisch B., Platzer B., Plachter B. 1990; Generation and application of a monoclonal antibody raised against a recombinant cytomegalovirus-specific polypeptide. Klinische Wochenschrift 68:1003–1007
    [Google Scholar]
  20. Lathey J. L., Spector S. A. 1991; Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. Journal of Virology 65:6371–6375
    [Google Scholar]
  21. Lathey J. L., Wiley C. A., Verity M. A., Nelson J. A. 1990; Cultured human brain capillary endothelial cells are permissive for infection by human cytomegalovirus. Virology 176:266–273
    [Google Scholar]
  22. Ljungman P., Engelhard D., Link H., Biron P., Brandt L., Brunet S., Cardonnier C., Debusscher L., Delaurenzi A., Kolb H. J., Messina C., Newland A. C., Prentice H. G., Richard C., Ruutu T., Tilg H., Verdonck L. 1992; Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European bone marrow transplant group. Clinical Infectious Diseases 14:831–835
    [Google Scholar]
  23. Masih A. S., Woods G. L., Thiele G. M., Rennard S. I., Johansson S. L., Thompson A. B., Linder J. 1991; Detection of cytomegalovirus in bronchoalveolar lavage: a comparison of techniques. Modern Pathology 4:108–112
    [Google Scholar]
  24. Mazeron M. C., Jahn G., Plachter B. 1992; Monoclonal antibody E-13 (M-810) to human cytomegalovirus recognizes an antigen encoded by exon 2 of the major immediate early gene. Journal of General Virology 73:2699–2703
    [Google Scholar]
  25. Mocarski E. S. 1993; Cytomegalovirus biology and replication. In The Human Herpesviruses pp 173–226 Edited by Roizman B., Whitley R. J., Lopez C. New York: Raven Press;
    [Google Scholar]
  26. Myerson D., Hackman R. C., Nelson J. A., Ward D. C., McDougall J. K. 1984; Widespread presence of histologically occult cytomegalovirus. Human Pathology 15:430–439
    [Google Scholar]
  27. Percivalle E., Revello M. G., Vago L., Morini F., Gerna G. 1991; Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement. Journal of Clinical Investigation 92:663–670
    [Google Scholar]
  28. Peters B. S., Beck E. J., Anderson S., Coleman D., Coker R., Main J., Migdal C., Harris J. R., Pinching A. J. 1991; Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival. Journal of Infection 23:129–137
    [Google Scholar]
  29. Plachter B., Nordin M., Zweygberg-Wirgart B., Mach M., Stein H., Grillner L., Jahn G. 1992; The DNA-binding protein p52 of human cytomegalovirus reacts with monoclonal antibody CCH2 and associates with the nuclear membrane at late times after infection. Virus Research 24:265–276
    [Google Scholar]
  30. Reynolds-Kohler C., Jahn G., Lewis S. H., Nelson J. A. 1993; Human immunodeficiency virus infection of foetal tissue. In Local immunity in reproductive tract tissues pp 377–390 Edited by Griffin P. D., Johnson P. M. Oxford: Oxford University Press;
    [Google Scholar]
  31. Roberts W. H., Sneddon J. M., Waldman J., Stephens R. E. 1989; Cytomegalovirus infection of gastrointestinal endothelium demonstrated by simultaneous nucleic acid hybridization and immunohistochemistry. Archives of Pathology and Laboratory Medicine 113:461–464
    [Google Scholar]
  32. Sakr M., Hassanein T., Gavaler J., Abu-Elmagd K., Fung J., Gordon R., Starzl T., Van Thiel D. 1992; Cytomegalovirus infection of the upper gastrointestinal tract following liver transplantation-incidence, location, and severity in cyclosporine- and FK506-treated patients. Transplantation 53:786–791
    [Google Scholar]
  33. Schrier R. D., Nelson J. A., Oldstone M. B. 1985; Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science 230:1048–1051
    [Google Scholar]
  34. Schulman L. L., Rjeison D. S., Austin J. H., Rose E. A. 1991; Cytomegalovirus pneumonitis after cardiac transplantation. Archives of Internal Medicine 151:1118–1124
    [Google Scholar]
  35. Sinzger C., Plachter B., Stenglein S., Jahn G. 1993a; Immunohistochemical detection of different viral antigens in smooth muscle, stromal and epithelial cells from acute HCMV-gastritis. Journal of Infectious Diseases 167:1427–1432
    [Google Scholar]
  36. Sinzger C., Müntefering H., Löning T., Stöss H., Plachter B., Jahn G. 1993b; Cell types infected in human cytomegalovirus placentitis identified by immunohistochemical double staining. Virchows Archiv A Pathological Anatomy and Histopathology 423:249–256
    [Google Scholar]
  37. Stinski M. F. 1991; Molecular biology of cytomegalovirus replication. In Cytomegalovirus biology and infection pp 7–36 New York: Plenum;
    [Google Scholar]
  38. Taylor-Wiedeman J., Sissons J. G. P., Borysiewicz L. K., Sinclair J. H. 1991; Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. Journal of General Virology 72:2059–2064
    [Google Scholar]
  39. Taylor-Wiedeman J., Hayhurst G. P., Sissons J. G. P., Sinclair J. H. 1993; Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals. Journal of General Virology 74:265–268
    [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. Ullrich R., Heise W., Bergs C., L’age M., Riecken E. O., Zeitz M. 1992; Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract. Gut 33:1080–1084
    [Google Scholar]
  42. Van der Bu W., Torensma R., Van Son W. J., Anema J., Schirm J., Tegzess A. M., The T. H. 1988; Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes. Journal of Medical Virology 25:179–188
    [Google Scholar]
  43. Waldman W. J., Roberts W. H., Davis D. H., Williams M. V., Sedmak D. D., Stephens R. E. 1991; Preservation of natural endothelial cytopathogenicity of cytomegalovirus by propagation in endothelial cells. Archives of Virology 117:143–164
    [Google Scholar]
  44. Weiss R. L., Snow G. W., Schumann G. B., Hammond M. E. 1991; Diagnosis of cytomegalovirus pneumonitis on bronchoalveolar lavage fluid: comparison of cytology, immunofluorescence, and in situ hybridization with viral isolation. Diagnostic Cytopathology 7:243–247
    [Google Scholar]
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