Polyclonal Activation of B Cells by Lactate Dehydrogenase-Elevating Virus is Mediated by N-Glycans on the Short Ectodomain of the Primary Envelope Glycoprotein
The common strains of lactate dehydrogenase-elevating virus (LDV-P and LD-vx) are primary examples for viruses that cause a permanent polyclonal activation of B cells that results in IgG2a hyper-gammaglobulinemia and the generation of autoantibodies and circulating immune complexes in their host, the mouse (Notkins et al., 1966; Coutelier and van Snick, 1985; Li et al, 1990). Plasma IgG2a levels increase from generally below 0.5 mg/ml to 2-6 mg/ml by two weeks post infection (p.i.) and remain elevated thereafter (see later). LDV-P/vx cause life-long persistent viremic infections (see Fig. 1A) which are maintained by continuous rounds of replication in a renewable subpopulation of macrophages and resistance to host immune responses (Plagemann, 1996). Previous results have shown that the single neutralization epitope located on the short (about 30 amino acids long) ectodomain of the primary envelope glycoprotein, VP-3P, carries three large N-glycan chains in LDV-P and LDV-vx (see Fig. 1A insert) that suppress the immunogenicity of the epitope and impair antibody neutralization of the virions of these quasispecies (Chen et al, 2000; Plagemann et al., 1999). The present results indicate that the three N-glycans on the VP-3P ectodomains of LDV-P/vx also play a critical role in the polyclonal activation of B cells by these LDVs.
KeywordsLactate Recombination Polysaccharide Concanavalin Vermillion
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- Cafruny, W. A., Heruth, D. P., Jaqua, M. J., and Plagemann, P. G. W., 1986, 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. J. Med. Virol. 19:175–186.PubMedCrossRefGoogle Scholar
- Hu, B., Even, C., and 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 Immunol 5:27–38.PubMedCrossRefGoogle Scholar
- Janeway, C. A., Travers, P., Walport, M., and Capra, J. D., 1999, Immunobiology. 4th edn., pp. 3231–3323. Garland Publishing.Google Scholar
- Li, K., Schuler, T., Chen, Z., Glass, G. E. G., Childs, J. E., and Plagemann, P. G. W., 2000, Isolation of lactate dehydrogenase-elevating viruses from wild house mice and their biological and molecular characterization. Virus. Res., In press.Google Scholar
- Plagemann, P. G. W., 1996, Lactate dehydrogenase-elevating virus and related viruses. In Virology, 3rd edn, (B. N. Fields, D. M. Knipe, & P. M. Howley, eds) Raven Press, New York, pp. 1105–1120.Google Scholar
- Plagemann, P. G. W., Chen, Z., and Li., K., 1999, Polylactosaminoglycan chains on the ectodomain of the primary envelope glycoprotein of an arterivirus determine its neuropathogenicity, sensitivity to antibody neutralization and immunogenicity of the neutralization epitope. Curr.Top. Virol. 1:27–43.Google Scholar
- Plagemann, P. G. W., Rowland, R. R. R., Even, C., and Faaberg, K. S., 1995, Lactate dehydrogenase-elevating virus— an ideal persistent virus? Seminars in Immunopathobiol. 17:167–186.Google Scholar
- Rowland, R. R. R., Even, C., Anderson, G. W., Chen, Z., Hu, B., and 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 viremia or the polyclonal activation of B cells and immune complex formation. J. Gen. Virol. 75:1071–1081.PubMedCrossRefGoogle Scholar