Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 75, Issue 12

Down-regulation of integrin α1/1 expression and association with cell rounding in human cytomegalovirus-infected fibroblasts No Access

Abstract

Human cytomegalovirus (HCMV) causes a c.p.e. characterized by rounding of the infected cell. Since interactions with the extracellular matrix may be involved in the cell rounding, we have analysed the expression of integrins, which are the main cell surface receptors involved in cell-substrate adhesion and spreading. By FACS analysis, a selective decrease in cell surface expression of 1/1 integrin was observed in HCMV-infected fibroblasts. This decrease coincides with cell rounding. Immunoprecipitation studies and FACS analysis of permeabilized cells have further demonstrated that total levels of this integrin are decreased in infected cells, suggesting that the reduction in cell surface 1/1integrin is not due to a defect in transport to the surface. Furthermore, we have ruled out the possibility that the observed decrease in 1/1expression is caused by a cytokine released from the infected cells by showing that the reduction is abolished by inactivating the HCMV with u.v. irradiation, and that conditioned medium from HCMV-infected cells has no effect on expression of 1/1integrin in uninfected cells. Concomitant with the reduction in 1/1levels, the HCMV-infected fibroblasts show a reduced ability to adhere to laminin and collagen IV. Taken together the data indicate that synthesis of HCMV protein(s) causes a decreased assembly/expression of 1/1integrin, coincident with the well characterized morphological alterations of the infected cell.

  • Received:
  • Accepted:
  • Published Online:
© The Journal of General Virology 1994
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-12-3319
1994-12-01
2025-12-07

Metrics

Loading full text...

Full text loading...

References

  1. Adams J. C., Watt F. M. 1989; Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature; London: 340307–309
     [Google Scholar]
  2. Albrecht T., Boldogh I., Fons M., Lee C. H., Abu Baker S., Russell J. M., Au W. W. 1989; Cell-activation responses to cytomegalovirus infection: relationship to the phasing of CMV replication and to the induction of cellular damage. Subcellular Biochemistry 15:157–202
     [Google Scholar]
  3. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. 1978; Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens -new tools for genetic analysis. Cell 14:9–20
     [Google Scholar]
  4. Bergelson J. M., Shepley M. P., Chan B. M. C., Hemler M. E., Finberg R. W. 1992; Identification of the integrin VLA-2 as a receptor for echovirus I. Science 255:1718–1720
     [Google Scholar]
  5. Borysiewicz L. K., Morris S., Page J. D., Sissons J. G. P. 1983; Human cytomegalovirus specific cytotoxic T lymphocytes -requirements for in vitro generation and specificity. European Journal of Immunology 13:804–809
     [Google Scholar]
  6. Briesewitz R., Epstein M. R., Marcantonio E. E. 1993; Expression of native and truncated forms of the human integrin α1 subunit. Journal of Biological Chemistry 268:2989–2996
     [Google Scholar]
  7. Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. 1990; The role of integrins α2/β1 and α3/β1 in cell-cell and cell-substrate adhesion of human epidermal cells. Journal of Cell Biology 110:1387–1404
     [Google Scholar]
  8. Cheresh D. A., Harper J. 1987; Arg-Gly-Asp recognition by a cell adhesion receptor requires its 130 kDa subunit. Journal of Biological Chemistry 262:1434–1437
     [Google Scholar]
  9. Cheresh D. A., Spiro R. C. 1987; Biosynthetic and functional properties of an Arg-Gly-Asp directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. Journal of Biological Chemistry 262:17703–17711
     [Google Scholar]
  10. Clyman R. I., Turner D. C., Kramer R. H. 1990; An alphal/ beta 1-like integrin receptor on rat aortic muscle cells mediates adhesion to laminin and collagen types 1 and IV. Arteriosclerosis 10:402–410
     [Google Scholar]
  11. Defilippi P., Silengo L., Tarone G. 1992; α6/β1 integrin (laminin receptor) is down-regulated by tumour necrosis factor α and interleukin-1β in human endothelial cells. Journal of Biological Chemistry 267:18303–18307
     [Google Scholar]
  12. Forsberg E., Paulsson M., Timpl R., Johansson S. 1990; Characterization of a laminin receptor on rat hepatocytes. Journal of Biological Chemistry 265:6376–6381
     [Google Scholar]
  13. Gullberg D., Turner D. C., Terracio L., Borg T. K., Rubin K. 1990; Different β1 -integrin collagen receptors on rat hepatocytes and cardiac fibroblasts. Experimental Cell Research 190:254–264
     [Google Scholar]
  14. Hall D. E., Reichardt L. F., Crowley E., Holley B., Moezzi H., Sonnenberg A., Damsky C. H. 1990; The αl/βl and α6/β1 integrin heterodimers mediate cell attachment to distinct sites on laminin. Journal of Cell Biology 110:2175–2184
     [Google Scholar]
  15. Heino J., Ignotz R. A., Hemler M. A., Crouse C., Massague J. 1989; Regulation of cell adhesion receptors by transforming growth factor beta. Journal of Biological Chemistry 264:380–388
     [Google Scholar]
  16. Hemler M. E., Sanchez-Madrid F., Flotte T. J., Krensky A. M., Burakoff J. J., Bhan A. K., Springer T. A., Strominger J. L. 1984; Glycoproteins of 210,000 and 130,000 M.W. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. Journal of Immunology 132:3011–3018
     [Google Scholar]
  17. Hemler M. E., Huang C., Schwarz L. 1987; The VLA protein family: characterization of five distinct cell surface heterodimers each with a common 130,000 Mr subunit. Journal of Biological Chemistry 262:3300–3309
     [Google Scholar]
  18. Ho M. 1991 Cytomegalovirus: Biology and Infection, 2nd edn. New York: Plenum Press;
     [Google Scholar]
  19. Hynes R. O. 1992; Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69:11–25
     [Google Scholar]
  20. Ignatius M. J., Reichardt L. F. 1988; Identification of a neuronal laminin receptor: an Mr 200/120 kD integrin heterodimer that binds laminin in a divalent cation-dependent manner. Neuron 1:713–725
     [Google Scholar]
  21. Jones T. R., Muzithras V. P. 1992a; A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. Journal of Virology 66:2541–2546
     [Google Scholar]
  22. Jones T. R., Muzithras V. P. 1992b; Expression from the IRS1 gene region is required for human cytomegalovirus-induced early rounding of fibroblasts. Proceedings from the 17th International Herpesvirus Workshop
     [Google Scholar]
  23. Kramer R. H., Marks N. 1989; Identification of integrin collagen receptors on human melanoma cells. Journal of Biological Chemistry 264:4684–4688
     [Google Scholar]
  24. Menko A. S., Boettiger D. 1987; Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation. Cell 51:51–57
     [Google Scholar]
  25. Rossino P., Defilippi P., Silengo L., Tarone G. 1991; Up-regulation of the integrin α1/β1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin. Cell Regulation 2:1021–1033
     [Google Scholar]
  26. Ruoslahti E., Pierschbacher M. D. 1986; Arg-Gly-Asp:-a versatile cell recognition signal. Cell 44:517–518
     [Google Scholar]
  27. Sanchez-Madrid F., De Landazuri M. O., Morago G., Cebrian M., Acevedo A., Bernabea C. 1986; VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterisation. European Journal of Immunology 16:1343–1349
     [Google Scholar]
  28. Santala P., Heino J. 1991; Regulation of integrin-type cell adhesion receptors by cytokines. Journal of Biological Chemistry 266:23505–23509
     [Google Scholar]
  29. Sonnenberg A., Jannsen H., Hogervorst F., Calafat J., Hilgers J. 1987; A complex of platelet glycoproteins Ic and Ha identified by a rat monoclonal antibody. Journal of Biological Chemistry 262:10376–10383
     [Google Scholar]
  30. Visser M. R., Vercellotti G. M., McCarthy J. B., Goodman J. L., Herbst T. J., Furcht L. T., Jacob H. S. 1989; Herpes simplex virus inhibits endothelial cell attachment and migration to extracellular matrix proteins. American Journal of Pathology 134:223–230
     [Google Scholar]
  31. Wahl S. M., Allen J. B., Weeks B. S., Wong H. L., Klotman P. E. 1993; Transforming growth factor β enhances integrin expression and type IV collagenase secretion in human monocytes. Proceedings of the National Academy of Sciences, U.S.A 90:4577–4581
     [Google Scholar]
  32. Wayner E. A., Carter W. G., Piotrowicz R. S., Kunicki T. J. 1988; The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoprotein Ic-IIa. Journal of Cell Biology 107:1881–1891
     [Google Scholar]
  33. Weeks B. S., Klotman M. E., Dhawan S., Kibbey M., Rappaport J., Kleinman H. K., Yamada K. M., Klotman P. E. 1991; HIV-1 infection of human T lymphocytes results in enhanced α5βl integrin expression. Journal of Cell Biology 114:847–853
     [Google Scholar]
  34. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. 1989; Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. Journal of Cell Biology 109:877–889
     [Google Scholar]
  35. Wickham T. J., Mathias P., Cheresh D. A., Nemerow G. R. 1993; Integrins αv/β3 and αv/β5 promote adenovirus internalization but not virus attachment. Cell 73:309–319
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-75-12-3319
Loading
Down-regulation of integrin α1/β1 expression and association with cell rounding in human cytomegalovirus-infected fibroblasts
J. Gen. Virol. 75, 3319 (1994); https://doi.org/10.1099/0022-1317-75-12-3319
/content/journal/jgv/10.1099/0022-1317-75-12-3319
/content/journal/jgv/10.1099/0022-1317-75-12-3319
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