1887

Abstract

Syncytium formation and subsequent generalized cell fusion have been reported as potentially important mechanisms of virus-induced cytotoxic effects. We tried to clarify the roles of fusion regulatory factor-1 (FRP-1) in virus-induced cell fusion. Two mutated human FRP-1/CD98 proteins [FRP-1/ HN, in which the cytoplasmic domain was replaced with the cytoplasmic domain of human parainfluenza virus type 2 (HPIV-2) haemagglutinin- neuraminidase (HN), and FRP-1/330 (serine), in which a cysteine at amino acid 330 was mutated to serine], when expressed stably in L cells, were lacking in cell-fusion-enhancing activity stimulated by anti-FRP-1 antibodies. Anti-FRP-1 antibodies enhanced Newcastle disease virus (NDV)-mediated polykaryocyte formation in parent HeLa cells, while anti-FRP-1 antibodies showed no/low effect on polykaryocyte formation in NDV-infected HeLa cells constitutively expressing FRP-1/HN (HeLa-FRP-1/ HN cells), indicating that the FRP-1/HN molecule is capable of acting as a dominant negative inhibitor. Furthermore, when HeLa-FRP-1/HN cells were infected with various rubulaviruses (HPIV-2, mumps virus, simian viruses 5 and 41), virus-induced cell fusion was also suppressed, although virus replication was not inhibited in these cells, showing that FRP-1 molecules are required for virus-induced cell fusion. Therefore, FRP-1 is considered to be related to the pathogenesis of paramyxoviruses.

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1997-04-01
2022-05-23
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References

  1. Friedman A. W., Diaz L. A., Moore J., Schaller J., Fox D. A. 1994; The human 4F2 antigen: evidence for cryptic and noncryptic epitopes and for a role of 4F2 in human T lymphocyte activation. Cellular Journal of Immunology 154:253–263
    [Google Scholar]
  2. Hashimoto Y., Masuko T., Yagita H., Endho N., Kanazawa J., Tazawa J. 1983; A proliferation-associated rat cell surface antigen recognized by a murine monoclonal antibody. Gann 74:819–821
    [Google Scholar]
  3. Haynes B. F., Hemler M. E., Mann D. L., Eisenbarth G. S., Shelhamer M. E., Mostowski H. S., Thomas C. A., Strominger J. L., Fauci A. S. 1981; Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. Journal of Immunology 126:1409–1414
    [Google Scholar]
  4. Hemler M. E., Strominger J. L. 1982; Characterization of the antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines. Journal of Immunology 131:334–340
    [Google Scholar]
  5. Ito Y., Tsurudome M., Hishiyama M. 1987a; The polypeptides of human parainfluenza type 2 virus and their synthesis in infected cells. Archives of Virology 95: 211–224
    [Google Scholar]
  6. Ito Y., Tsurudome M., Yamada A., Hishiyama M. 1987b; Induction of cell fusion in Newcastle disease virus-infected L929 cells by anti-L729 cell antisera. Journal of General Virology 68: 1261–1266
    [Google Scholar]
  7. Ito Y., Komada H., Kusagawa S., Tsurudome M., Matsumura H., Kawano M., Ohta H., Nishio M. 1992; Fusion regulation proteins on the cell surface : isolation and characterization of monoclonal antibodies which enhance giant polykaryocyte formation in Newcastle disease virus-infected cell lines of human origin. Journal of Virology 66:5999–6007
    [Google Scholar]
  8. Kawano M., Bando H., Yuasa T., Kondo K., Tsurudome M., Komada H., Nishio M. 1990; Sequence determination of the hemagglutinin-neuraminidase (HN) gene of human parainfluenza type 2 virus and the construction of a phylogenetic tree for HN proteins of all the paramyxoviruses that are infectious to humans. Virology 174:308–313
    [Google Scholar]
  9. MacDonald H. R., Lees R. K., Bron C. J. 1985; Cell surface glycoprotein involved in the stimulation of interleukin 1-dependent characterization by monoclonal antibodies. Journal of Immunology 135:3944–3950
    [Google Scholar]
  10. Michalak M., Quackenbush E. J., Letarte L. 1986; Inhibition of Na+/Ca2+ exchanger activity in cardia and skeletal muscle sarcolemnal vesicles by monoclonal antibody 44D7. Journal of Biological Chemistry 261:92–95
    [Google Scholar]
  11. Nagai Y., Ito Y., Hamaguchi M., Yoshida T., Matsumoto T. 1981; Relation of interferon production to the limited replication of Newcastle disease virus in L cells. Journal of General Virology 55:109–116
    [Google Scholar]
  12. Ohgimoto S., Tabata N., Suga S., Nishio M., Ohta H., Tsurudome M., Komada H., Kawano M., Watanabe N., Ito Y. 1995; Molecular characterization of fusion regulatory protein-I (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160- mediated cell fusion: FRP-1 and 4F2/CD98 are identical molecules. Journal of Immunology 135:3585–3592
    [Google Scholar]
  13. Ohta H., Tsurudome M., Matsumura H., Koga Y., Morikawa S., Kawano M., Kusagawa S., Komada H., Nishio M., Ito Y. 1994; Molecular and biological characterization of fusion regulatory proteins (FRPs) : anti-FRP MAbs induced HIV-mediated cell fusion via an integrin system. EMBO Journal 13:2044–2055
    [Google Scholar]
  14. Quackenbush E., Clabby M., Gottesdiener K. M., Barbosa J., Jones N. H., Strominger J. L., Speck S., Leiden J. M. 1987; Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth. Proceedings of the National Academy of Sciences USA: 846526–6530
    [Google Scholar]
  15. Spagnoll G. C., Ausiello C., Palma C., Bellone G., Ippoliti G., Letarte M., Malavasi F. 1991; Functional effects of a monoclonal antibody directed against a distinct epitope on 4F2 molecular complex in human peripheral blood mononuclear cell activation. Cellular Immunology 136:208–218
    [Google Scholar]
  16. Tabata N., Ito M., Shimokata K., Suga S., Tsurudome M., Kawano M., Matsumura H., Komada H., Nishio M., Ito Y. 1995; Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes : induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies. Journal of Immunology 153:3256–3266
    [Google Scholar]
  17. Teixeira S., DiGrandi S., Kuhn L. C. 1987; Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus. Journal of Biological Chemistry 20:9574–9580
    [Google Scholar]
  18. Tsurudome M., Nishio M., Komada H., Bando H., Ito Y. 1989; Extensive antigenic diversity among human parainfluenza type 2 virus isolates and immunological relationships among paramyxoviruses revealed by monoclonal antibodies. Virology 171:38–48
    [Google Scholar]
  19. Wacholtz M. C., Cragoe E. J., Lipsky P. E. 1992; A Na+-dependent Ca2+ exchanger generates the sustained increase in intracellular Ca2+required for T cell activation. Journal of Immunology 149:1912–1920
    [Google Scholar]
  20. Wells R. G., Lee W. S., Kanai Y., Leiden J. M., Hediger M. A. 1992; The 4F2 antigen heavy chain induces uptake of neutral and dibasic amino acids in Xenopus oocytes. Journal of Biological Chemistry 267:15285–15288
    [Google Scholar]
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