1887

Abstract

The common biologically cloned isolates of lactate dehydrogenase-elevating virus (LDV-P and LDV-vx) invariably cause a polyclonal activation of B cells in immunocompetent mice. It is recognized by an at least 10-fold increase in plasma IgG2a levels and the formation of immune complexes that most likely consist of autoantibodies and their antigens. The present study indicates that three closely spaced -glycans on the short ectodomain of the primary envelope glycoprotein, VP-3P, of LDV-P/vx, play a major role in inducing the polyclonal proliferation of B cells. IFN-γ then seems to mediate the differentiation of the activated B cells to IgG2a-producing plasma cells. These conclusions are based on the finding that the IgG2a hypergammaglobulinaemia and immune complex formation were much lower in mice that were infected with LDV variants (LDV-C and LDV-v) whose VP-3P ectodomains lack two of the three -glycans than in LDV-P/vx infected mice. In contrast, the VP-3P ectodomains of three neutralization escape variants of LDV-C/v whose VP-3P ectodomains possess three -glycosylation sites caused a polyclonal activation of B cells comparable to that of LDV-P/vx.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-9-2167
2000-09-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/9/0812167a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-9-2167&mimeType=html&fmt=ahah

References

  1. Ahmed R., Oldstone M. B. A. 1984; Mechanisms and biological implications of virus-induced B-cell activation. In Concepts in Viral Pathogenesis pp 231–238 Edited by Notkins A. L., Oldstone M. B. A. New York: Springer Verlag;
    [Google Scholar]
  2. Anderson G. W., Rowland R. R. R., Palmer G. A., Even C., Plagemann P. G. W. 1995; Lactate dehydrogenase-elevating virus replication persists in liver, spleen, lymph node, and testis tissues and results in accumulation of viral RNA in germinal centers concomitant with polyclonal activation of B cells. Journal of Virology 69:5177–5185
    [Google Scholar]
  3. Cafruny W. A., Chan S. P. K., Harty J. T., Yousefi S., Kowalchyk K., McDonald D., Foreman B., Budweg G., Plagemann P. G. W. 1986a; Antibody response of mice to lactate dehydrogenase-elevated virus during infection and immunization with inactivated virus. Virus Research 5:357–375
    [Google Scholar]
  4. Cafruny W. A., Heruth D. P., Jaqua M. J., Plagemann P. G. W. 1986b; Immunoglobulins that bind to uncoated ELISA plates: appearance in mice during infection with lactate dehydrogenase-elevating virus and in human anti-nuclear antibody-positive sera. Journal of Medical Virology 19:175–186
    [Google Scholar]
  5. Cafruny W. A., Bradley S. E., Rowland R. R. R. 1999; Regulation of immune complexes during infection of mice with lactate dehydrogenase-elevating virus: studies with interferon-gamma gene knockout and tolerant mice. Viral Immunology 12:163–173
    [Google Scholar]
  6. Chen Z., Plagemann P. G. W. 1997; Detection of lactate dehydrogenase-elevating virus in transplantable mouse tumors by biological assay and RT–PCR assays and its removal from the tumor cells. Journal of Virological Methods 65:227–236
    [Google Scholar]
  7. Chen Z., Rowland R. R. R., Anderson G. W., Palmer G. A., Plagemann P. G. W. 1997; Coexistence in lactate dehydrogenase-elevating virus pools of variants that differ in neuropathogenicity and ability to establish a persistent infection. Journal of Virology 71:2910–2920
    [Google Scholar]
  8. Chen Z., Li K., Rowland R. R. R., Anderson G. W., Plagemann P. G. W. 1998; Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired ability for high viremic persistent infection. Journal of Neurovirology 4:560–568
    [Google Scholar]
  9. Chen Z., Li K., Rowland R. R. R., Plagemann P. G. W. 1999; Selective antibody neutralization prevents neuropathogenic lactate dehydrogenase-elevating virus from causing paralytic disease in immunocompetent mice. Journal of Neurovirology 5:200–208
    [Google Scholar]
  10. Chen Z., Li K., Plagemann P. G. W. 2000; Neuropathogenicity and sensitivity to antibody neutralization of lactate dehydrogenase-elevating virus are determined by polylactosaminoglycan chains on the primary envelope glycoprotein. Virology 266:88–98
    [Google Scholar]
  11. Coutelier J.-P., van Snick J. 1985; Isotypically restricted activation of B lymphocytes by lactic dehydrogenase virus. European Journal of Immunology 15:250–255
    [Google Scholar]
  12. Coutelier J.-P., van der Logt J. T. M., Haesen F. W. A., Vink A., van Snick J. 1988; Virally induced modulation of murine IgG antibody subclasses. Journal of Experimental Medicine 168:2373–2378
    [Google Scholar]
  13. Coutelier J.-P., Coulie P. G., Wauters P., Heremans H., van der Logt J. T. M. 1990; In vivo polyclonal B-lymphocyte activation elicited by murine viruses. Journal of Virology 64:5383–5388
    [Google Scholar]
  14. Coutelier J.-P., van Broek J., Wolf S. F. 1995; Interleukin-12 gene expression after viral infection in the mouse. Journal of Virology 69:1955–1958
    [Google Scholar]
  15. Even C., Hu B., Erickson L., Plagemann P. G. W. 1992; Correlation between levels of immunoglobulins and immune complexes in plasma of C57BL/6 and C57L/J mice infected with MAIDS retrovirus. Viral Immunology 5:39–50
    [Google Scholar]
  16. Faaberg K. S., Plagemann P. G. W. 1995; The envelope proteins of lactate dehydrogenase-elevating virus and their membrane topography. Virology 212:512–525
    [Google Scholar]
  17. Faaberg K. S., Plagemann P. G. W. 1997; ORF3 of lactate dehydrogenase-elevating virus encodes a soluble, nonstructural, highly glycosylated, and antigenic protein. Virology 227:245–251
    [Google Scholar]
  18. Godeny E. K., Chen L., Kumar S. N., Methven S. L., Koonin E. V., Brinton M. A. 1993; Complete genomic sequence and phylogenetic analysis of the lactate dehydrogenase-elevating virus (LDV). Virology 194:585–596
    [Google Scholar]
  19. Harty J. T., Chan S. P. K., Plagemann P. G. W. 1987; Characteristics of monoclonal antibodies to the lactate dehydrogenase-elevating virus. Intervirology 27:53–60
    [Google Scholar]
  20. Hu B., Even C., Plagemann P. G. W. 1992; Immune complexes that bind to ELISA plates not coated with antigen in mice infected with lactate dehydrogenase-elevating virus: relationship to IgG2a and IgG2b-specific polyclonal activation of B cells. Viral Immunology 5:27–38
    [Google Scholar]
  21. Janeway C. A., Travers P., Walport M., Capra J. D. 1999 Immunobiology, 4th edn. pp 321–323 Garland Publishing;
  22. Li X., Hu B., Harty J. T., Even C., Plagemann P. G. W. 1990; Polyclonal activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes. Viral Immunology 3:273–288
    [Google Scholar]
  23. Li K., Chen Z., Plagemann P. G. W. 1998; The neutralization epitope of lactate dehydrogenase-elevating virus is located on the short ectodomain of the primary envelope glycoprotein. Virology 242:239–245
    [Google Scholar]
  24. Li K., Chen Z., Plagemann P. G. W. 1999; High frequency genetic recombination of an arterivirus, lactate dehydrogenase-elevating virus, in mice and evolution of neuropathogenic variants. Virology 258:73–83
    [Google Scholar]
  25. Li K., Schuler T., Chen Z., Glass G. E. G., Childs J. E., Plagemann P. G. W. 2000; Isolation of lactate dehydrogenase-elevating viruses from wild house mice and their biological and molecular characterization. Virus Research (in press
    [Google Scholar]
  26. Notkins A. L., Mergenhagen S. E., Rizzo A. A., Scheele C., Waldmann T. A. 1966; Elevated γ globulin and increased antibody production in mice infected with lactic dehydrogenase virus. Journal of Experimental Medicine 123:347–356
    [Google Scholar]
  27. Palmer G. A., Kuo L., Chen Z., Faaberg K. S., Plagemann P. G. W. 1995; Sequence of genome of lactate dehydrogenase-elevating virus: heterogeneity between strains P and C. Virology 209:637–642
    [Google Scholar]
  28. Plagemann P. G. W. 1996; Lactate dehydrogenase-elevating virus and related viruses. In Fields Virology pp 1105–1120 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  29. Plagemann P. G. W., Rowland R. R. R., Even C., Faaberg K. S. 1995; Lactate dehydrogenase-elevating virus – an ideal persistent virus?. Seminars in Immunopathology 17:167–186
    [Google Scholar]
  30. Rowland R. R. R., Even C., Anderson G. W., Chen Z., Hu B., Plagemann P. G. W. 1994; Neonatal infection of mice with lactate dehydrogenase-elevating virus results in suppression of humoral antiviral immune response but does not alter the course of viraemia or the polyclonal activation of B cells and immune complex formation. Journal of General Virology 75:1071–1081
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-9-2167
Loading
/content/journal/jgv/10.1099/0022-1317-81-9-2167
Loading

Data & Media loading...

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