1887

Abstract

SUMMARY

SUMMARY We have previously demonstrated that human cytomegalovirus (CMV) binds the host protein microglobulin ( m) from body fluids or from cell culture media. In this report we have examined the effect of the m on viral infectivity. We have shown that the addition of human purified m, or a fraction of foetal calf serum corresponding to bovine m, to culture medium increased the amount of infectious extracellular CMV, compared to that from cells grown in serum-free medium. Metabolic labelling experiments demonstrated that this effect was not due to an increase in the amount of extracellular virus but to an increase in the infectivity of the virus present in extracellular fluids. We concluded that the binding of m by CMV increased its infectivity. We have shown that CMV and m compete for binding sites on fibroblasts. As the main binding site on cells for /Cm is the class IHLA heavy chain we compared the binding of CMV to the Raji and Daudi cell lines which express or lack expression of class I HLA molecules. The binding of radiolabelled m-coated CMV was significantly higher to Raji cells than to Daudi cells. Furthermore, CMV could compete with m for binding to Raji cells, although the reverse was not true. These results demonstrate that CMV can use class I HLA molecules as a virus receptor. We propose that when coated with Cm, CMV has the capacity to displace m from the class I HLA heavy chain-m dimer on the cell surface and bind to cells. The fact that m enhances infectivity suggests that such binding leads to productive infection of cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-68-3-793
1987-03-01
2021-10-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/68/3/JV0680030793.html?itemId=/content/journal/jgv/10.1099/0022-1317-68-3-793&mimeType=html&fmt=ahah

References

  1. Bernabeu C., Van De Rijn M., Lerch P. G. 1984; β 2m from serum associates with Class I antigens on the surface of cultured cells. Nature; London: 308642–645
    [Google Scholar]
  2. Brodsky F. M., Parham P., Barnstable C. J., Crumpton M. J., Bodmer W. F. 1979; Monoclonal antibodies for analysis of the HLA system. Immunological Reviews 47:3–61
    [Google Scholar]
  3. Chalmer J. E. 1980; Genetic resistance to murine cytomegalovirus infection. In Genetic Control of Natural Resistance to Infection and Malignancy pp 283–290 Skamene E. Edited by New York: Academic Press;
    [Google Scholar]
  4. Chalmer J. E., Mackenzie J. s., Stanley N. F. 1977; Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. Journal of General Virology 37:107–114
    [Google Scholar]
  5. Cresswell P., Springer T., Strominger J. L., Turner M. J., Grey H. M., Kubo R. T. 1974; Immunological identity of the small subunit of HLA-A antigens and /J2-microglobulin and its turnover on the cell membrane. Proceedings of the National Academy of Sciences U.S.A.: 712123–2127
    [Google Scholar]
  6. De Préval C., Mach B. 1983; The absence of β 2-microglobulin in Daudi cells: active gene but inactive messenger RNA. Immunogenetics 17:133–140
    [Google Scholar]
  7. Fraker P. J., Speck J. c. 1978; Protein and cell membrane iodinations with a sparingly soluble chloramide 1,2,4,6-tetrachloro-3a,6a-diphenyl glycoluril. Biochemical and Biophysical Research Communications 80:849–857
    [Google Scholar]
  8. Griffiths P. D., Panjwani D. D., Stirk P. R., Ball M. G., Ganczakowski M., Blacklock H. A., Prentice H. G. 1984; Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by detection of early antigen fluorescent foci. Lancet ii:1242–1245
    [Google Scholar]
  9. Grundy(CHALMER) J. E., Mackenzie J. s., Stanley N. F. 1981; Influence of H-2 and non H-2 genes on resistance to murine cytomegalovirus infection. Infection and Immunity 32:277–286
    [Google Scholar]
  10. Grundy J. E., McKeatlng J. A., Griffiths P. D. 1987; Cytomegalovirus strain AD169 binds β 2 microglobulin in vitro after release from cells. Journal of General Virology 68:777–784
    [Google Scholar]
  11. Hyafil F., Strominger J. L. 1979; Dissociation and exchange of the β 2-microglobulin subunit of HLA-A and HLA-B antigens. Proceedings of the National Academy of Sciences U S A: 765834–5838
    [Google Scholar]
  12. Kefford R. F., Calabi F., Fearnley I. M., Burrone O. R., Milstein C. 1984; Serum β-microglobulin binds to a T-cell differentiation antigen and increases its expression. Nature; London: 308641–645
    [Google Scholar]
  13. Mckeating J. A., Grundy J. E., Varghese Z., Griffiths P. D. 1986; Detection of cytomegalovirus by ELISA in urine samples is inhibited by β-microglobulin. Journal of Medical Virology 18:341–348
    [Google Scholar]
  14. Mckeating J. A., Griffiths P. D., Grundy J. E. 1987; Cytomegalovirus in urine specimens has host microglobulin bound to the viral envelope: a mechanism of evading the host immune response?. Journal of General Virology 68:785–792
    [Google Scholar]
  15. Pereira L., Hoffman M., Gallo D., Cremer N. 1982; Monoclonal antibodies to human cytomegalovirus: three surface membrane proteins with unique immunological and electrophoretic properties specify cross-reactive determinants. Infection and Immunity 36:924–932
    [Google Scholar]
  16. Potter T. A., Boyer C., Schmitt-Verhulst A-M., Goldstein P., Rajan T. v. 1984; Expression of H-2Db on the cell surface in the absence of detectable β 2-microglobulin. Journal of Experimental Medicine 160:317–322
    [Google Scholar]
  17. Potter T. A., Zeff R. A., Schmitt-Verhulst A-M., Rajan T. V. 1985; Molecular analysis of an EL4 cell line that expresses H-2Db but not H-2Kb or β-microglobulin. Proceedings of the National Academy of Sciences U.S.A.: 822950–2954
    [Google Scholar]
  18. Sanderson A. R., Ward P. J., Mccance D., Kyold J., Underwood J., Mowbray J., Callard J., Allen W. R. 1985; A novel way of visualising major histocompatibility complex I molecules from many species. Transplantation Proceedings 17:965–968
    [Google Scholar]
  19. Sege K., Rask R., Peterson P. A. 1981; Role of β-microglobulin in the intracellular processing of HLA antigens. Biochemistry 20:4523–4530
    [Google Scholar]
  20. Talbot P., Almeida J. D. 1977; Human cytomegalovirus: purification of enveloped virions and dense bodies. Journal of General Virology 36:345–349
    [Google Scholar]
  21. Ward P. J., Sanderson A. R. 1983; The interchange of derivatives of human β 2 microglobulin in HLA alloantigens. Immunology 48:87–92
    [Google Scholar]
  22. Ziegler A., Milstein C. 1979; A small polypeptide different from β 2 microglobulin associated with a human cell surface antigen. Nature; London: 279243–244
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-68-3-793
Loading
/content/journal/jgv/10.1099/0022-1317-68-3-793
Loading

Data & Media loading...

Most cited this month 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