1887

Abstract

We have isolated new MAbs directed against the human fusion regulatory protein 1 (FRP-1; CD98) molecule using human FRP-1-expressing L929 cells as antigens. The biological activities, and in particular the human immunodeficiency virus (HIV)-mediated fusion regulatory activity of seven anti-FRP-1/CD98 MAbs were analysed using the U937/gp160 cell line, which is a CD4 U937 cell line expressing HIV gp160. Two MAbs induced multi-nucleated giant cell formation in U937/gp160 cells and the other five MAbs showed no fusion-inducing ability. However, four of these MAbs suppressed multinucleated giant cell formation of U937/gp160 cells induced by the activating anti-FRP-1 MAbs. Interestingly, five of the MAbs induced multi-nucleated giant cells in peripheral blood monocytes and one MAb showing fusion-inducing ability in U937/gp160 cells suppressed multinucleated giant cell formation of monocytes induced by anti-FRP-1 MAbs. Furthermore, four of the anti-FRP-1 MAbs suppressed cell fusion of Jurkat/gp160 cells, which are Jurkat cells expressing HIV gp160. Thus, FRP-1/CD98 is capable of either activating or inhibiting HIV-mediated cell fusion depending on whether an enhancing or inhibiting antibody is used, indicating that FRP-1/CD98 is a multipotential molecule. Thus, HIV-mediated cell fusion can be regulated by modification of the FRP-1 system. Furthermore, the present study demonstrates that the FRP-1 and FRP-2 systems are interdependent.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-11-2747
1996-11-01
2021-10-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/11/JV0770112747.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-11-2747&mimeType=html&fmt=ahah

References

  1. Ashorn P. A., Berger E. A., Moss B. 1990; Human immunodeficiency virus envelope glycoprotein/CD4 mediated fusion of nonprimate cells with human cells. Journal of Virology 64:2149–2156
    [Google Scholar]
  2. Barre-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., CHamaret S., Gruest J., Dauguet C., Axler-Blin C., Brun-Bezinet F., Rouzioux C., Rozenbaum W., Montagnier L. 1983; Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome (AIDS). Science 220:868–871
    [Google Scholar]
  3. Bron C., Rousseaux M., Spiazzi A., MacDonald H. R. 1986; Structural homology between the human 4F2 antigen and a murine cell surface glycoprotein associated with lymphocyte activation. Journal of Immunology 137:397–399
    [Google Scholar]
  4. Connor R. I., Ho D. D. 1994; Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression. Journal of Virology 68:4400–4408
    [Google Scholar]
  5. Dalgleish A. G., Beverly P. C. L., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. 1984; The CD4 (T-4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–766
    [Google Scholar]
  6. Fouchier R. A. M., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., Miedema F., Schuitemaker H. 1992; Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gpl20. Journal of Virology 66:3183–3187
    [Google Scholar]
  7. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Saafai B., White G., Foster P., Markaham P. D. 1984; Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS. Science 224:500–503
    [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. Hoxie J. A., Alpers J. D., Rackowski J. L., Huebner K., Haggarty B. S., Cedarbaum A. J., Reed J. C. 1986; Alteration in T4(CD4) protein synthesis and mRNA synthesis in cells infected with HIV. Science 234:1123–1127
    [Google Scholar]
  12. Ito Y., Tsurudome M., Yamada A., Hishiyama M. 1987a; Induction of cell fusion in Newcastle disease virus-infected L929 cells by anti-L929 cell antisera. Journal of General Virology 68:1261–1266
    [Google Scholar]
  13. Ito Y., Tsurudome M., Hishiyama M. 1987b; The polypeptides of human parainfluenza type 2 virus and their synthesis in infected cells. Archives of Virology 95:211–224
    [Google Scholar]
  14. Ito Y., Tsurudome M., Bando H., Komada H., Nishio M. 1989; Incomplete replication of human parainfluenza virus type 2 in mouse L929 cells. Archives of Virology 108:137–144
    [Google Scholar]
  15. 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]
  16. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckmann J. C., Montagnier L. 1984; T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767–768
    [Google Scholar]
  17. Koga Y., Sasaki M., Yoshida H., Wigzell H., Kimura G., Nomoto K. 1990; Cytopathic effect determined by the amount of CD4 molecules in human cell lines expressing envelope glycoprotein of HIV. Journal of Immunology 144:94–102
    [Google Scholar]
  18. Koga Y., Sasaki M., Yoshida H., Tsu O., Kimura G., Nomoto K. 1991; Disturbance of nuclear transport of protein in CD4+ cells expressing gp160 of human immunodeficiency virus. Journal of Virology 65:5609–5612
    [Google Scholar]
  19. Koot M., Keet I. P. M., Vos A. H. V., Goede R. E. Y., Roos M. T. L., Coutinho R. A., Miedema F., Schellekens P. T. A., Tersmette M. 1993; Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Annals of Internal Medicine 118:681–688
    [Google Scholar]
  20. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. 1984; Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 225:840–842
    [Google Scholar]
  21. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. 1986a; Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 323:725–728
    [Google Scholar]
  22. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. 1986b; AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232:1123–1127
    [Google Scholar]
  23. McClure M. O., Marsh M., Weiss R. A. 1988; Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism. EMBO Journal 7:513–518
    [Google Scholar]
  24. McNearney T., Hornickova Z., Markham R., Birdwell A., Arens M., Saah A., Ratner L. 1992; Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. Proceedings of the National Academy of Sciences, USA 89:10247–10251
    [Google Scholar]
  25. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. 1988; The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333–348
    [Google Scholar]
  26. Matsumaya T., Kobayashi N., Yamamoto N. 1991; Cytokines and HIV infection: is AIDS a tumor necrosis factor disease?. AIDS 5:1405–1417
    [Google Scholar]
  27. Nakao M., Kubo K., Hara A., Hirohashi N., Futagami E., Shichijo S., Sagawa K., Itoh K. 1993; A monoclonal antibody (H227) recognizing a new epitope of 4F2 molecular complex associated with T cell activation. Cellular Immunology 152:226–233
    [Google Scholar]
  28. Ohgimoto S., Tabata N., Suga S., Nishio M., Ohta H., Tsurodome M., Komada H., Kawano M., Watanabe N., Ito Y. 1995; Molecular characterization of fusion regulatory protein-1 (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]
  29. 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]
  30. Patterson J. A. K., Eisinger M., Haynes B. F., Berger C. L., Edelson R. L. 1984; Monoclonal antibody 4F2 reactive with basal layer keratinocytes: studies in the normal and a hyperproliferative state. Journal of Investigative Dermatology 83:210–213
    [Google Scholar]
  31. 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 84:6526–6530
    [Google Scholar]
  32. Rosenberg Z. F., Fauci A. S. 1990; Immunopathogenesis mechanism of HIV infection: cytokine induction of HIV expression. Immunology Today 11:176–180
    [Google Scholar]
  33. Schuitemaker H., Kootstra N. A., de Goede R. E. Y., de Wolf F., Miedema F., Tersmette M. 1991; Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants and syncytium-inducing ability in primary T-cell culture. Journal of Virology 65:356–363
    [Google Scholar]
  34. Schuitemaker H., Koot M., Kootstra N., Dercksen M. W., Goede R. T. D., Steenwijk R., Lange J. M. A., Schattenkerk J. K., Miedema F., Tersmette M. 1992; Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus populations. Journal of Virology 66:1354–1360
    [Google Scholar]
  35. Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A. 1986; Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322:470–474
    [Google Scholar]
  36. Somasundaran M., Zapp M. L., Beattie L. K., Pang L., Byron K. S., Bassell G. J., Sullivan J. L., Singer R. H. 1994; Localization of HIV RNA in mitochondria of infected cells: potential role in cytopathogenicity. Journal of Cell Biology 126:1353–1360
    [Google Scholar]
  37. Spagnoll G. C., Ausiello C., Palma G., Bellone G., Ippoliti G., Letarte M., Maiavasi 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]
  38. Stein B. S., Gowda S. D., Lifson J. D., Penhallow R. G., Bensch K. G., Engleman E. G. 1987; pH-Independent HIV entry into CD4positive T cells via virus envelope fusion to the plasma membrane. Cell 49:659–668
    [Google Scholar]
  39. Tabata N., Ito M., Shimokata K., Suga S., Ohgimoto S., Tsurudome M., Kawano M., Matsumura H., Komada H., Nishio M., Ito Y. 1995a; 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]
  40. Tabata N., Yoshida T., Shiraishi T., Suga S., Tsurudome M., Ito Y. 1995b; Tissue distribution of fusion regulatory protein-1 and fusion regulatory protein-2. Archives of Pathology and Laboratory Medicine 119:461–466
    [Google Scholar]
  41. Teixeira S., Di Grandi 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]
  42. Terai G., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. 1991; Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. Journal of Clinical Investigation 87:1710–1715
    [Google Scholar]
  43. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. 1989; Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. Journal of Virology 63:2118–2125
    [Google Scholar]
  44. 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]
  45. Yagita H., Masuko T., Hashimoto Y. 1986a; Inhibition of tumor cell growth in vitro by murine monoclonal antibodies that recognize a proliferation-associated cell surface antigen system in rats and humans. Cancer Research 46:1478–1484
    [Google Scholar]
  46. Yagita H., Masuko T., Takahashi N., Hashimoto Y. 1986b; Monoclonal antibodies that inhibit activation and proliferation of lymphocytes. 1. Expression of the antigen on monocytes and activated lymphocytes. Journal of Immunology 136:2055–2061
    [Google Scholar]
  47. Zhang L. Q., Mackenzie P., Cleland A., Holmes E. G., Brown A. J. L., Simmonds P. 1993; Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. Journal of Virology 67:3345–3356
    [Google Scholar]
  48. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. 1993; Genotypic and phenotypic characterization of HIV-1 in patients with primary infection. Science 261:1179–1181
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-11-2747
Loading
/content/journal/jgv/10.1099/0022-1317-77-11-2747
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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