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Neutralization of MHV-A59 by Soluble Recombinant Receptor Glycoproteins

  • Bruce D. Zelus
  • David R. Wessner
  • Gabriela S. Dveksler
  • Kathryn V. Holmes
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 440)

Abstract

The interaction of viruses with specific receptors is an important determinant of viral tissue tropism and species specificity. Our goals are to understand how mouse hepatitis virus (MHV) recognizes its cellular receptor, MHVR, and how post-binding interactions with this receptor influence viral fusion and entry. Murine cells express a variety of cell surface molecule in the biliary glycoprotein (Bgp) family that are closely related to the MHVR. When these proteins are expressed at high levels in cell culture, they function as MHV receptors. We used a baculovirus expression system to produce soluble recombinant murine Bgp receptors in which the transmembrane and cytoplasmic domains have been re-placed with a six-histidine tag. The soluble glycoproteins were purified to apparent homo-geneity and shown to react with antisera to the native receptor. We compared the virus neutralizing activities of various soluble receptor glycoproteins. Soluble MHVR [sMHVR(1–4)] had 10–20 fold more virus neutralizing activity the soluble protein derived from the Bgplb glycoprotein [sBgplb(1–4)], from MHV-resistant SJL mice. The sMHVR(1–4) glycoprotein was 60–100 fold more active than a truncated receptor mole-cule containing only the first two immunoglobulin-like domains, sMHVR(l,2). The obser-vation that sMHVR lacking domains 3 and 4 neutralizes MHV-A59 very poorly suggests that these domains may influence virus binding or subsequent steps associated with neutralization.

Keywords

Soluble Receptor Virus Neutralize Tissue Tropism Baculovirus Expression System Mouse Hepatitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Barthold, S.W., 1986, Mouse hepatitis virus: biology and epizootiology, in: Viral and mycoplasma infections of laboratory rodents. Effects on biomedical research, (P.N. Bhatt, R.O. Jacoby, H.C. Morse III and A.E. New, eds.), Academic Press, Orlando, FL, pp. 571–601.CrossRefGoogle Scholar
  2. Benchimol, S., Fuks, A., Jothy, A., Beauchemin, N., Shirota, K., and Stanners, CR, 1989, Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule, Cell 57:327–334.PubMedCrossRefGoogle Scholar
  3. Boyle, J.F., Weismiller, D.G., and Holmes, K.V., 1987, Genetic resistance to Mouse Hepatitis Virus correlates with absence of virus-binding activity on target tissues, J. Virol. 61:185–189.PubMedGoogle Scholar
  4. Brümmendorf, T., and Rathjen, F.G., 1994, Introduction, in: Cell Adhesion Molecules 1: immunoglobulin superfa-mily, (P. Sheterline, ed.), Academic Press, London, pp. 951–962.Google Scholar
  5. Chen, D.S., Asanaka, M., Yokomori, K., Wang, F., Hwang, S.B., Li, H.P., and Lai, M.M., 1995, A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus, Proc. Natl. Acad. Sci. USA 92:12095–12099.PubMedCrossRefGoogle Scholar
  6. Collins, A.R., Knobler, R.L., Powell, H., and Buchmeier, M.J., 1982, Monoclonal antibodies to murine hepatitis virus-4 (strain JHM) define the viral glycoprotein responsible for attachment and cell-cell fusion, Virology 119:358–371.PubMedCrossRefGoogle Scholar
  7. Colston, E.M. and Racaniello, V.R., 1995, Poliovirus variants selected on mutant receptor-expressing cells identify capsid residues that expand receptor recognition, J. Virol. 69:4823–4829.PubMedGoogle Scholar
  8. Coutelier, J., Godfraind, C, Dveksler, G.S., Wysocka, M., Cardellichio, C.B., and Nöel, H., 1994, B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as recep-tors for murine coronoavirus, Eur. J. Immunol. 24:1383–1390.PubMedCrossRefGoogle Scholar
  9. Devaux, P., Buchholz, C.J., Schneider, U., Escoffier, C, Cattaneo, R., and Gerlier, D., 1997, CD46 Short Consen-sus Repeats III and IV enhance Measles Virus binding but impair soluble hemagglutinin binding, J. Virol. 71:4157–4160.PubMedGoogle Scholar
  10. Dveksler, G.S., Pensiero, M.N., Cardellichio, C.B., Williams, R.K., Jiang, G.S., Holmes, K.V., and Dieffenbach, C.W., 1991, Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV, J. Virol. 65:6881–6891.PubMedGoogle Scholar
  11. Dveksler, G.S., Dieffenbach, C.W., Cardellichio, C.B., McCuaig, K., Pensiero, M.N., Jiang, G.S., Beauchemin, N., and Holmes, K.V., 1993, Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the Coronavirus mouse hepatitis virus-A59, J. Virol. 67:1–8.PubMedGoogle Scholar
  12. Dveksler, G.S., Pensiero, M.N., Dieffenbach, C.W., Cardellichio, C.B., Basile, A.A., Elia, P.E., and Holmes, K.V., 1993, Mouse hepatitis virus strain A59 and blocking antireceptor monoclonal antibody bind to the N-termi-nal domain of cellular receptor, Proc. Natl. Acad. Sei. USA 90:1716–1720.CrossRefGoogle Scholar
  13. Dveksler, G.S., Gagneten, S.E., Scanga, C.A., Cardellichio, C.B., and Holmes, K.V., 1996, Expression of the recombinant anchorless N-terminal domain of mouse hepatitis virus (MHV) receptor makes hamster of hu-man cells susceptible to MHV infection, J. Virol. 70:4142–4145.PubMedGoogle Scholar
  14. Frana, M.F., Behnke, J.N., Sturman, L.S., and Holmes, K.V., 1985, Proteolytic cleavage of the E2 glycoprotein of murine Coronavirus: host-dependent differences in proteolytic cleavage and cell fusion, J. Virol. 56:912–920.PubMedGoogle Scholar
  15. Godfraind, C, Langreth, S.G., Cardellichio, C.B., Knobler, R., Coutelier, J.P., Dubois-Dalcq, M., and Holmes, K.V, 1995, Tissue and cellular distribution of an adhesion molecule in the carcinoembryonic antigen fam-ily that serves as a receptor for mouse hepatitis virus, Lab. Invest. 73:615–627.PubMedGoogle Scholar
  16. Greve, J.M., Forte, CR, Mador, C.W., Meyer, A.M., Hoover-Litty, H., Wunderlich, D., and McClelland, A., 1991, Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1, J. Virol. 65:6015–6023.PubMedGoogle Scholar
  17. Kaplan, G., Freistadt, M.S., and Racaniello, V.R., 1990, Neutralization of Poliovirus by Cell Receptors Expressed in Insect Cells, J. Virol. 64:4697–4702.PubMedGoogle Scholar
  18. McCuaig, K., Rosenberg, M., Nedéllec, P., Turbide, C, and Beauchemin, N., 1993, Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms, Gene 127:173–183.PubMedCrossRefGoogle Scholar
  19. Nedellec, P., Dveksler, G.S., Daniels, E., Turbide, C, Chow, B., Basile, A.A., Holmes, K.V., and Beauchemin, N., 1994, Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative re-ceptor for mouse hepatitis viruses, J. Virol. 68:4525–4537.PubMedGoogle Scholar
  20. Ohtsuka, N., Yamada, Y.K., and Taguchi, F., 1996, Difference in virus-binding activity of two distinct receptor proteins for mouse hepatitis virus, Journal of General Virology 77:1683–1692.PubMedCrossRefGoogle Scholar
  21. Pasick, J.M., Wilson, G.A., Morris, V.L., and Dales, S., 1992, SJL/J resistance to mouse hepatitis virus-JHM-in-duced neurologic disease can be partially overcome by viral variants of S and host immunosuppression, Microbial Pathogenesis. 13:1–15.PubMedCrossRefGoogle Scholar
  22. Rao, P.V., and Gallagher, T.M., 1997, Identification of a contiguous 6-residue determinant in the MHV receptor that controls the level of virion binding to cells, Virology 229:336–348.PubMedCrossRefGoogle Scholar
  23. Rudert, F., Saunders, A.M., Rebstock, S., Thompson, J. A., and Zimmerman, W., 1992, Characterization of murine carcinoembryonic antigen gene family members, Mam. Genome 3:262–273.CrossRefGoogle Scholar
  24. Sturman, L.S., Ricard, CS., and Holmes, K.V., 1990, Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion, J. Virol. 64:3042–3050.PubMedGoogle Scholar
  25. Wege, H., Siddell, S., and ter Meulan, V, 1982, The biology and pathogenisis of coronaviruses, Curr. Top. in Microbiol. Immunol. 99:165–200.CrossRefGoogle Scholar
  26. Wessner, D.R., Shick, P.C., Lu, J.-H., Cardellichio, C.B., Gagneten, S.E., Beauchemin, N., Holmes, K.V., and Dveksler, G.S., 1997, Mutational Analysis of the Virus and Monoclonal Antibody Binding Sites in MHVR, the Cellular Receptor of the Murine Corona Virus MHV-A59, J. Virol. In Press.Google Scholar
  27. Williams, R.K., Jiang, G.S., and Holmes, K.V., 1991, Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins, Proc. Natl. Acad. Sci. USA 88:5533–5536.PubMedCrossRefGoogle Scholar
  28. Yokomori, K., and Lai, M.M., 1992, The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection, J. Virol. 66:6931–6938.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Bruce D. Zelus
    • 1
  • David R. Wessner
    • 2
  • Gabriela S. Dveksler
    • 2
  • Kathryn V. Holmes
    • 1
    • 2
  1. 1.Health Sciences Center Denver, Department of MicrobiologyUniversity of ColoradoDenverUSA
  2. 2.Department of PathologyUniformed Services University of the Health SciencesBethesdaUSA

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