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.
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References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Wege, H., Siddell, S., and ter Meulan, V, 1982, The biology and pathogenisis of coronaviruses, Curr. Top. in Microbiol. Immunol. 99:165–200.
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.
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.
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.
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Zelus, B.D., Wessner, D.R., Dveksler, G.S., Holmes, K.V. (1998). Neutralization of MHV-A59 by Soluble Recombinant Receptor Glycoproteins. In: Enjuanes, L., Siddell, S.G., Spaan, W. (eds) Coronaviruses and Arteriviruses. Advances in Experimental Medicine and Biology, vol 440. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5331-1_1
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