1887

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Volume 85, Issue 7

Downregulation of the cellular adhesion molecule Thy-1 (CD90) by cytomegalovirus infection of human fibroblasts Free

Abstract

The deregulation of cellular adhesion molecules by human cytomegalovirus (HCMV) appears to be correlated with the development of vascular disease. In this study, it was investigated whether the expression of Thy-1 (CD90), a member of the immunoglobulin superfamily of adhesion molecules with constitutive expression on fibroblast cells, is modulated following infection with HCMV. It was observed that Thy-1 cell surface expression decreased significantly during the course of infection. Addition of neutralizing antibodies, as well as UV inactivation of virus, prevented Thy-1 downregulation. In contrast, inhibition of virus replication by cidofovir did not alter Thy-1 regulation by HCMV, indicating that immediate-early (IE) and/or early (E) gene products are responsible. Interestingly, after infection of fibroblasts with a recombinant GFP-expressing virus, infected as well as non-infected cells showed a reduced Thy-1 cell surface expression. From these findings, it is concluded that IE or E gene products of HCMV induce a so far unidentified soluble factor that mediates Thy-1 downregulation.

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2004-07-01
2024-04-20
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References

  1. Abeysinghe H. R., Cao Q., Xu J., Pollock S., Veyberman Y., Guckert N. L., Keng P., Wang N. 2003; THY1 expression is associated with tumor suppression of human ovarian cancer. Cancer Genet Cytogenet 143:125–132 [CrossRef]
     [Google Scholar]
  2. Ahn K., Angulo A., Ghazal P., Peterson P. A., Yang Y., Fruh K. 1996; Human cytomegalovirus inhibits antigen presentation by a sequential multistep process. Proc Natl Acad Sci U S A 93:10990–10995 [CrossRef]
     [Google Scholar]
  3. Alcami A., Koszinowski U. H. 2000; Viral mechanisms of immune evasion. Mol Med Today 6:365–372 [CrossRef]
     [Google Scholar]
  4. Alford C. A., Stagno S., Pass R. F., Britt W. J. 1990; Congenital and perinatal cytomegalovirus infections. Rev Infect Dis Suppl 7:S745–S753
     [Google Scholar]
  5. Almeida G. D., Porada C. D., St Jeor S., Ascensao J. L. 1994; Human cytomegalovirus alters interleukin-6 production by endothelial cells. Blood 83:370–376
     [Google Scholar]
  6. Boldogh I., AbuBakar S., Albrecht T. 1990; Activation of proto-oncogenes: an immediate early event in human cytomegalovirus infection. Science 247:561–564 [CrossRef]
     [Google Scholar]
  7. Borchers A. T., Perez R., Kaysen G., Ansari A. A., Gershwin M. E. 1999; Role of cytomegalovirus infection in allograft rejection: a review of possible mechanisms. Transpl Immunol 7:75–82 [CrossRef]
     [Google Scholar]
  8. Craig W., Kay R., Cutler R. L., Lansdorp P. M. 1993; Expression of Thy-1 on human hematopoietic progenitor cells. J Exp Med 177:1331–1342 [CrossRef]
     [Google Scholar]
  9. Fairley J. A., Baillie J., Bain M., Sinclair J. H. 2002; Human cytomegalovirus infection inhibits epidermal growth factor (EGF) signalling by targeting EGF receptors. J Gen Virol 83:2803–2810
     [Google Scholar]
  10. Fortunato E. A., McElroy A. K., Sanchez I., Spector D. H. 2000; Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus. Trends Microbiol 8:111–119 [CrossRef]
     [Google Scholar]
  11. Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. 1989; Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA 261:3561–3566 [CrossRef]
     [Google Scholar]
  12. Grundy J. E., Lawson K. M., MacCormac 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. J Infect Dis 177:1465–1474 [CrossRef]
     [Google Scholar]
  13. Jun Y., Kim E., Jin M., Sung H. C., Han H., Geraghty D. E., Ahn K. 2000; Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules. J Immunol 164:805–811 [CrossRef]
     [Google Scholar]
  14. Kronschnabl M., Stamminger T. 2003; Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site. J Gen Virol 84:61–73 [CrossRef]
     [Google Scholar]
  15. Lautenschlager I., Soots A., Krogerus L. 7 other authors; 1999; Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model. Intervirology 42:279–284 [CrossRef]
     [Google Scholar]
  16. Lee W. S., Jain M. K., Arkonac B. M. 8 other authors 1998; Thy-1, a novel marker for angiogenesis upregulated by inflammatory cytokines. Circ Res 82:845–851 [CrossRef]
     [Google Scholar]
  17. Lemstrom K., Koskinen P., Hayry P. 1995; Molecular mechanisms of chronic renal allograft rejection. Kidney Int Suppl 52:S2–S10
     [Google Scholar]
  18. Martelius T., Krogerus L., Hockerstedt K., Bruggeman C., Lautenschlager I. 1998; Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts. Hepatology 27:996–1002 [CrossRef]
     [Google Scholar]
  19. Muhlestein J. B., Horne B. D., Carlquist J. F., Madsen T. E., Bair T. L., Pearson R. R., Anderson J. L. 2000; Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation 102:1917–1923 [CrossRef]
     [Google Scholar]
  20. Murayama T., Ohara Y., Obuchi M., Khabar K. S., Higashi H., Mukaida N., Matsushima K. 1997; Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF- κ B-binding sites of the interleukin-8 gene. J Virol 71:5692–5695
     [Google Scholar]
  21. Ohizumi Y., Suzuki H., Matsumoto Y., Masuho Y., Numazaki Y. 1992; Neutralizing mechanisms of two human monoclonal antibodies against human cytomegalovirus glycoprotein 130/55. J Gen Virol 73:2705–2707 [CrossRef]
     [Google Scholar]
  22. Phillips A. J., Tomasec P., Wang E. C., Wilkinson G. W., Borysiewicz L. K. 1998; Human cytomegalovirus infection downregulates expression of the cellular aminopeptidases CD10 and CD13. Virology 250:350–358 [CrossRef]
     [Google Scholar]
  23. Saalbach A., Aneregg U., Bruns M., Schnabel E., Herrmann K., Haustein U. F. 1996; Novel fibroblast-specific monoclonal antibodies: properties and specificities. J Invest Dermatol 106:1314–1319 [CrossRef]
     [Google Scholar]
  24. Saalbach A., Kraft R., Herrmann K., Haustein U. F., Anderegg U. 1998; The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1. Arch Dermatol Res 290:360–366 [CrossRef]
     [Google Scholar]
  25. Saalbach A., Haustein U. F., Anderegg U. 2000; A ligand of human thy-1 is localized on polymorphonuclear leukocytes and monocytes and mediates the binding to activated thy-1-positive microvascular endothelial cells and fibroblasts. J Invest Dermatol 115:882–888 [CrossRef]
     [Google Scholar]
  26. Saalbach A., Hildebrandt G., Haustein U. F., Anderegg U. 2002; The thy-1/thy-1 ligand interaction is involved in binding of melanoma cells to activated thy-1-positive microvascular endothelial cells. Microvasc Res 64:86–93 [CrossRef]
     [Google Scholar]
  27. Schaarschmidt P., Reinhardt B., Michel D. & 10 ther authors; 1999; Altered expression of extracellular matrix in human-cytomegalovirus-infected cells and a human artery organ culture model to study its biological relevance. Intervirology 42:357–364 [CrossRef]
     [Google Scholar]
  28. Sharom F. J., Lehto M. T. 2002; Glycosylphosphatidylinositol-anchored proteins: structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem Cell Biol 80:535–549 [CrossRef]
     [Google Scholar]
  29. Simmen K. A., Singh J., Luukkonen B. G., Lopper M., Bittner A., Miller N. E., Jackson M. R., Compton T., Fruh K. 2001; Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B. Proc Natl Acad Sci U S A 98:7140–7145 [CrossRef]
     [Google Scholar]
  30. Speir E., Modali R., Huang E. S., Leon M. B., Shawl F., Finkel T., Epstein S. E. 1994; Potential role of human cytomegalovirus and p53 interaction in coronary restenosis [see comments]. Science 265:391–394 [CrossRef]
     [Google Scholar]
  31. Spencer J. V., Lockridge K. M., Barry P. A., Lin G., Tsang M., Penfold M. E., Schall T. J. 2002; Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. J Virol 76:1285–1292 [CrossRef]
     [Google Scholar]
  32. Steinhoff G., You X. M., Steinmuller C., Boeke K., Stals F. S., Bruggeman C. A., Haverich A. 1995; Induction of endothelial adhesion molecules by rat cytomegalovirus in allogeneic lung transplantation in the rat. Scand J Infect Dis Suppl 99:58–60
     [Google Scholar]
  33. Waldman W. J., Knight D. A., Huang E. H. 1998; An in vitro model of T cell activation by autologous cytomegalovirus (CMV)-infected human adult endothelial cells: contribution of CMV-enhanced endothelial ICAM-1. J Immunol 160:3143–3151
     [Google Scholar]
  34. Wang X., Huong S. M., Chiu M. L., Raab-Traub N., Huang E. S. 2003; Epidermal growth factor receptor is a cellular receptor for human cytomegalovirus. Nature 424:456–461 [CrossRef]
     [Google Scholar]
  35. Warren A. P., Ducroq D. H., Lehner P. J., Borysiewicz L. K. 1994; Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes. J Virol 68:2822–2829
     [Google Scholar]
  36. Yilmaz S., Koskinen P. K., Kallio E., Bruggeman C. A., Hayry P. J., Lemstrom K. B. 1996; Cytomegalovirus infection-enhanced chronic kidney allograft rejection is linked with intercellular adhesion molecule-1 expression. Kidney Int 50:526–537 [CrossRef]
     [Google Scholar]
  37. Yurochko A. D., Huang E. S. 1999; Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression. J Immunol 162:4806–4816
     [Google Scholar]
  38. Yurochko A. D., Mayo M. W., Poma E. E., Baldwin A. S. Jr, Huang E. S. 1997; Induction of the transcription factor Sp1 during human cytomegalovirus infection mediates upregulation of the p65 and p105/p50 NF- κ B promoters. J Virol 71:4638–4648
     [Google Scholar]
  39. Zhou Y. F., Leon M. B., Waclawiw M. A., Popma J. J., Yu Z. X., Finkel T., Epstein S. E. 1996; Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 335:624–630 [CrossRef]
     [Google Scholar]
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Downregulation of the cellular adhesion molecule Thy-1 (CD90) by cytomegalovirus infection of human fibroblasts
J. Gen. Virol. 85, 1995 (2004); https://doi.org/10.1099/vir.0.79818-0
/content/journal/jgv/10.1099/vir.0.79818-0
/content/journal/jgv/10.1099/vir.0.79818-0
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