1887

Abstract

Cytotoxic T cell recognition of virus-infected cells requires the presentation of viral peptides by class I HLA molecules on the cell surface. We report here that cytomegalovirus (CMV) infection of human fibroblasts results in a progressive decrease in the cell surface expression of class I HLA and β-microglobulin (βm) such that in the late stages of infection the majority of infected cells have no detectable surface class I HLA. Coincident with decreased surface expression of class I HLA was an increase in his cytoplasmic expression. Confocal scanning laser microscopic analysis demonstrated that class I HLA and βm accumulate in a perinuclear compartment inside the CMV-infected cell. Our data thus support the concept that CMV infection induces altered transport of class I HLA to the cell surface. We suggest that the virus has evolved this mechanism as a strategy to avoid T cell recognition of infected cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-9-2395
1992-09-01
2021-10-27
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/9/JV0730092395.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-9-2395&mimeType=html&fmt=ahah

References

  1. Andersson M., Paabo S., Nilsson T., Peterson P. A. 1985; Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance. Cell 43:215–222
    [Google Scholar]
  2. Andreoni M., Faircloth M., Vugler L., Britt W. J. 1989; A rapid microneutralization assay for the measurement of neutralizing antibody reactive with human cytomegalovirus. Journal of Virologi-cal Methods 23:157–167
    [Google Scholar]
  3. Barnes P., Rose J. S. L., Grundy J. E. 1990a; Alterations in levels of class I HLA antigens in cytomegalovirus-infected cells. Abstracts of the 10th Meeting of the European Federation of Immunological Societies, Edinburgh abstract 30-3
    [Google Scholar]
  4. Barnes P., Rose J. S. L., Grundy J. E. 1990b; Altered expression of class I HLA antigens in cytomegalovirus infected cells. In Abstracts of the VIIIth International Congress of Virology, Berlin p 175
    [Google Scholar]
  5. Beck S., Barrell B. G. 1988; Human cytomegalovirus encodes a glycoprotein homologous to MHC class-I antigens. Nature, London 331:269–272
    [Google Scholar]
  6. Borysiewicz L. K., Graham S., Hickling J. K., Mason P. D., Sissons J. G. 1988a; Human cytomegalovirus-specific cytotoxic T cells: their precursor frequency and stage specificity. European Journal of Immunology 18:269–275
    [Google Scholar]
  7. Borysiewicz L. K., Hickling J. K., Graham S., Sinclair J., Cranage M. P., Smith G. L., Sissons J. G. 1988b; Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. Journal of Experimental Medicine 168:919–931
    [Google Scholar]
  8. Britt W. J., Auger D. 1986; Synthesis and processing of the envelope gp55-116 complex of human cytomegalovirus. Journal of Virology 58:185–191
    [Google Scholar]
  9. Brodsky F. M., Parham P. 1982; Monomorphic anti-HLA A, B, C monoclonal antibody detecting molecular subunits and combinatorial determinants. Journal of Immunology 128:129–135
    [Google Scholar]
  10. Browne H., Smith G., Beck S., Minson T. 1990; A complex between the MHC class I homologue encoded by human cytomegalovirus and beta 2 microglobulin. Nature, London 347:770–772
    [Google Scholar]
  11. Burgert H.-G., Maryanski J. L., Kvist S. 1987; E3/19K protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proceedings of the National Academy of Sciences, U.S.A. 84:1356–1360
    [Google Scholar]
  12. Downes K., Grundy J. C. 1992; Upregulation of LFA-3 and ICAM-1 on the surface of fibroblasts infected with cytomegalovirus. Immunology (in press)
    [Google Scholar]
  13. Griffiths P. D., Grundy J. E. 1987; Molecular biology and immunology of cytomegalovirus. Biochemical Journal 241:313–324
    [Google Scholar]
  14. Grundy J. E. 1991; The immune response to cytomegalovirus. In Progress in Cytomegalovirus Research pp 143–155 Edited by Landini M. P. Amsterdam: Elsevier;
    [Google Scholar]
  15. Grundy J. E., McKeating 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]
  16. Grundy J. E., Ayles H. M., McKeating J. A., Butcher R. G., Griffiths P. D., Poulter L. W. 1988; Enhancement of class I HLA antigen expression by cytomegalovirus: role in amplification of virus infection. Journal of Medical Virology 25:483–495
    [Google Scholar]
  17. Hutchinson K., Eren E., Grundy J. E. 1991; Expression of ICAM-1 and LFA-3 following cytomegalovirus infection. In Progress in Cytomegalovirus Research pp 267–270 Edited by Landini M. P. Amsterdam: Elsevier;
    [Google Scholar]
  18. Koszinowski U. H., Keil G. M., Schwarz H., Schickedanz J., Reddehase M. J. 1987; A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes. Journal of Experimental Medicine 166:289–294
    [Google Scholar]
  19. Lampson L. A., Fisher C. A., Whelan J. P. 1983; Striking paucity of HLA-A, B, C and beta-2-microglobulin on human neuroblastoma cell lines. Journal of Immunology 130:2471–2478
    [Google Scholar]
  20. Liabeuf A., De Kaouel C.Le B., Kourilsky F. M., Malissen B., Manuel Y., Sanderson A. R. 1981; An antigenic determinant of human β 2-microglobulin masked by the association with HLA heavy chains at the cell surface analysis by monoclonal antibodies. Journal of Immunology 127:1542–1548
    [Google Scholar]
  21. Lindsley M. D., Torpey D. J., Rinaldo C. R. J. 1986; HLA-DR-restricted cytotoxicity of cytomegalovirus-infected monocytes mediated by Leu-3-positive T cells. Journal of Immunology 136:3045–3051
    [Google Scholar]
  22. Reddehase M. J., Mutter W., Munch K., Buhring H. J., Koszinowski U. H. 1987; CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. Journal of Virology 61:3102–3108
    [Google Scholar]
  23. Schrier P. I., Bernards R., Vaessen T. M. J., Houiweling A., van der Eb A. J. 1983; Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. Nature, London 305:771–775
    [Google Scholar]
  24. Signas C., Katze M. G., Persson H., Philipson L. 1982; An adenovirus glycoprotein binds heavy chains of class I transplantation antigens from man and mouse. Nature, London 299:175–178
    [Google Scholar]
  25. van Dorp W. T., Jonges E., Bruggeman C. A., Daha M. R., van Es L. A., van der Woude F. J. 1989; Direct induction of MHC class I, but not class II, expression on endothelial cells by cytomegalovirus infection. Transplantation 48:469–472
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-9-2395
Loading
/content/journal/jgv/10.1099/0022-1317-73-9-2395
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