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Volume 82, Issue 6

selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells Free

Abstract

Four human cytomegalovirus (HCMV) isolates from different clinical sources were extensively propagated in human embryonic lung fibroblasts (HELF). Plaque isolates from each of the four virus strains were evaluated for their ability to be transferred to polymorphonuclear leukocytes (PMNL) and to grow in endothelial cells (EC). While all four of the clinical strains were found to be both PMNL- and EC-tropic, variants were identified from each of the four strains that lacked both biological properties, while three of the four parental strains lost their transfer capacity before passage 50 in HELF. It was demonstrated that one of the four field isolates (VR6110) and its transfer-deficient variant were genetically related, but showed different curves of virus yield in HELF. In addition, neither the immediate-early (IE) mRNA nor the IE protein p72 were found to be transferred to PMNL before 72 h post-infection (late in infection) or in the presence of viral DNA replication inhibitors. These findings link EC and PMNL tropism and suggest that PMNL tropism is a late HCMV function.

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© Microbiology Society
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/content/journal/jgv/10.1099/0022-1317-82-6-1429
2001-06-01
2024-04-26
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References

  1. Baldanti F., Sarasini A., Furione M., Gatti M., Comolli G., Revello M. G., Gerna G. 1998; Coinfection of the immunocompromised but not the immunocompetent host by multiple human cytomegalovirus strains. Archives of Virology 143:1701–1709
     [Google Scholar]
  2. Blok M. J., Christiaans M. H. L., Goossens V. J., van Hooff J. P., Top B., Middeldorp J. M., Bruggeman C. A. 1998a; Evaluation of a new method for early detection of active cytomegalovirus infections. A study in kidney transplant recipients. Transplant International 11:Suppl. 1107–109
     [Google Scholar]
  3. Blok M. J., Goossens V. J., Vanherle S. J. V., Top B., Tacken N., Middeldorp J. M., Christiaans M. H. L., van Hooff J. P., Bruggeman C. A. 1998b; Diagnostic value of monitoring human cytomegalovirus late pp67 mRNA expression in renal-allograft recipients by nucleic acid sequence-based amplification. Journal of Clinical Microbiology 36:1341–1346
     [Google Scholar]
  4. Blok M. J., Christiaans M. H. L., Goossens V. J., van Hooff J. P., Sillekens P., Middeldorp J. M., Bruggeman C. A. 1999; Early detection of human cytomegalovirus infection after transplantation by nucleic acid sequence-based amplification. Transplantation 67:1274–1277
     [Google Scholar]
  5. Cha T.-H., Tom E., Kemble G. W., Duke G. M., Mocarski E. S., Spaete R. S. 1996; Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. Journal of Virology 70:78–83
     [Google Scholar]
  6. Chandler S. H., McDougall J. K. 1986; Comparison of restriction site polymorphisms among clinical isolates and laboratory strains of human cytomegalovirus. Journal of General Virology 67:2179–2192
     [Google Scholar]
  7. Chou S. W. 1990; Differentiation of cytomegalovirus strains by restriction analysis of DNA sequences amplified from clinical specimens. Journal of Infectious Diseases 162:738–742
     [Google Scholar]
  8. Gerna G., Revello M. G., Percivalle E., Zavattoni M., Parea M., Battaglia M. 1990; Quantification of human cytomegalovirus viremia by using monoclonal antibodies to different viral proteins. Journal of Clinical Microbiology 28:2681–2688
     [Google Scholar]
  9. Gerna G., Zipeto D., Parea M., Revello M. G., Silini E., Percivalle E., Zavattoni M., Grossi P., Milanesi G. 1991; Monitoring of human cytomegalovirus infections and ganciclovir treatment in heart transplant recipients by determination of viremia, antigenemia and DNAemia. Journal of Infectious Diseases 164:488–498
     [Google Scholar]
  10. Gerna G., Zipeto D., Percivalle E., Parea M., Revello M. G., Maccario R., Peri G., Milanesi G. 1992a; 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]
  11. Gerna G., Revello M. G., Percivalle E., Morini F. 1992b; Comparison of different immunostaining techniques and monoclonal antibodies to the lower matrix phosphoprotein (pp65) for optimal quantitation of human cytomegalovirus antigenemia. Journal of Clinical Microbiology 30:1232–1237
     [Google Scholar]
  12. Gerna G., Furione M., Baldanti F., Sarasini A. 1994; Comparative quantitation of human cytomegalovirus DNA in blood leukocytes and plasma of transplant and AIDS patients. Journal of Clinical Microbiology 32:2709–2717
     [Google Scholar]
  13. Gerna G., Zavattoni M., Baldanti F., Sarasini A., Chezzi L., Grossi P., Revello M. G. 1998a; Human cytomegalovirus (HCMV) leukodnaemia correlates more closely with clinical symptoms than antigenemia and viremia in heart and heart–lung transplant recipients with primary HCMV infection. Transplantation 65:1378–1385
     [Google Scholar]
  14. Gerna G., Percivalle E., Torsellini M., Revello M. G. 1998b; Standardization of the human cytomegalovirus antigenemia assay by means of in vitro generated pp65-positive peripheral blood polymorphonuclear leukocytes. Journal of Clinical Microbiology 36:3585–3589
     [Google Scholar]
  15. Gerna G., Baldanti F., Middeldorp J. M., Furione M., Zavattoni M., Lilleri D., Revello M. G. 1999; Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung and bone marrow transplant recipients as determined by nucleic acid sequence-based amplification. Journal of Clinical Microbiology 37:902–911
     [Google Scholar]
  16. Gerna G., Percivalle E., Baldanti F., Sozzani S., Lanzarini P., Genini E., Lilleri D., Revello M. G. 2000; Human cytomegalovirus replicates abortively in polymorphonuclear leukocytes following transfer from infected endothelial cells via transient microfusion events. Journal of Virology 74:5629–5638
     [Google Scholar]
  17. Grefte A., Harmsen M. C., van der Giessen M., Knollema S., van Son W. J., The T. H. 1994; Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection. Journal of General Virology 75:1989–1998
     [Google Scholar]
  18. Grundy J. E., Lawson K. M., MacCormack L. P., Fletcher J. M., Yong K. L. 1998; Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil–endothelial cell contact and during neutrophil transendothelial migration. Journal of Infectious Diseases 177:1465–1474
     [Google Scholar]
  19. Kemble G., Duke G., Winter R., Spaete R. 1996; Defined large-scale alterations of the human cytomegalovirus genome constructed by cotransfection of overlapping cosmids. Journal of Virology 70:2044–2048
     [Google Scholar]
  20. MacCormack L. P., Grundy J. E. 1999; Two clinical isolates and the Toledo strain of cytomegalovirus contain endothelial cell tropic variants that are not present in the AD169, Towne or Davis strains. Journal of Medical Virology 57:298–307
     [Google Scholar]
  21. Middeldorp J. M., Adriaanse H., Van de Crommert J., Greijer A., Baldanti F., Gerna G., Verschuuren E., van der Bij W., The T. H., Sillekens P. 1999; Direct quantification of human cytomegalovirus (HCMV) immediate early and late mRNA levels in the blood of HCMV-infected individuals using competitive NASBA. 24th International Herpesvirus Workshop (MIT; Boston/Cambridge, MA, USA: Abstract 11.036
    [Google Scholar]
  22. Penfold M. E. T., Dairaghi D. J., Duke G. M., Saederup N., Mocarski E. S., Kemble G. W., Schall T. 1999; Cytomegalovirus encodes a potent chemokine. Proceedings of the National Academy of Sciences, USA 96:9839–9844
     [Google Scholar]
  23. Revello M. G., Percivalle E., Zavattoni M., Parea M., Grossi P., Gerna G. 1989; Detection of human cytomegalovirus immediate early antigen in leukocytes as a marker of viremia in immunocompromised patients. Journal of Medical Virology 29:88–93
     [Google Scholar]
  24. Revello M. G., Zavattoni M., Sarasini A., Percivalle E., Simoncini L., Gerna G. 1998a; Human cytomegalovirus in blood of immunocompetent persons during primary infection: prognostic implications for pregnancy. Journal of Infectious Diseases 177:1170–1175
     [Google Scholar]
  25. Revello M. G., Percivalle E., Arbustini E., Pardi R., Sozzani S., Gerna G. 1998b; In vitro generation of human cytomegalovirus pp65 antigenemia, viremia, and leukoDNAemia. Journal of Clinical Investigation 101:2686–2692
     [Google Scholar]
  26. Sinzger C., Schmidt K., Knapp J., Kahl M., Beck R., Waldman J., Hebart H., Einsele H., Jahn G. 1999; Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome. Journal of General Virology 80:2867–2877
     [Google Scholar]
  27. van den Berg A. P., Klompmaker I. J., Haagsma E. B., Scholten-Sampson A., Bijleveld C. M. A., Schirm J., van der Giessen M., Sloff M. J. H., The T. H. 1991; Antigenemia in the diagnosis and monitoring of active cytomegalovirus infection after liver transplantation. Journal of Infectious Diseases 164:265–270
     [Google Scholar]
  28. van der Bij W., Schirm J., Torensma R., van Son W. J., Tegzess A. M., The T. H. 1988; Comparison between viremia and antigenemia for detection of cytomegalovirus in blood. Journal of Clinical Microbiology 26:2531–2535
     [Google Scholar]
  29. Waldman W. J., Sneddon J. M., Stephens R. E., Roberts W. H. 1989; Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells. Journal of Medical Virology 28:223–230
     [Google Scholar]
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In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells
J. Gen. Virol. 82, 1429 (2001); https://doi.org/10.1099/0022-1317-82-6-1429
/content/journal/jgv/10.1099/0022-1317-82-6-1429
/content/journal/jgv/10.1099/0022-1317-82-6-1429
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