Abstract
AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population1. The causative agent of this disease is the human immunodeficiency virus, HIV2–4, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death5,6. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry7,8. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.
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References
Fahey, J. L. et al. Am. J. Med. 76, 95–100 (1984).
Barre-Sinoussi, F. et al. Science 220, 868–871 (1983).
Gallo, R. et al. Science 224, 500–503 (1984).
Levy, J. A. et al. Science 225, 840–842 (1984).
Lifson, J. D., Reyes, G. R., McGrath, M. G., Stein, B. S. & Engleman, E. G. Science 232, 1123–1127 (1986).
Lifson, J. D. et al. Nature 323, 725–728 (1986).
Stein, B. S. et al. Cell 49, 659–668 (1987).
Kowalski, M. et al. Science 237, 1351–1355 (1987).
Hoxie, J. A., Matthews, D. M., Callahan, K. J., Cassel, D. L. & Cooper, R. A. J. Immun. 137, 1194–1201 (1986).
Acres, R. B., Conlon, P. J., Mochizuki, D. Y. & Gallis, B. J. biol. Chem. 261, 16210–16214 (1986).
Weyand, C. M., Goronzy, J. & Fathman, C. G. J. Immun. 138, 1351–1354 (1987).
Hidaka, H., Inagaki, M., Kawamoto, S. & Sasaki, Y. Biochemistry 5036–5042 (1984).
McDougal, J. S. et al. J. Immun. 135, 3151–3162 (1985).
McDougal, J. S. et al. Science 231, 382–385 (1986).
Sodroski, J., Goh, W. C., Rosen, C., Campbell, K. & Haseltine, W. A. Nature 322, 470–474 (1986).
Dalgleish, A. G. et al. Nature 312, 763–766 (1984).
Klatzmann, D. et al. Nature 312, 767–768 (1984).
Maddon, P. J. et al. Cell 47, 333–348 (1986).
Sredni, B., Volkman, D., Schwartz, R. H. & Fauchi, A. S. in Isolation, Characterization and Utilization of T-Lymphocyte Clones (eds Fathman, C. G. & Fitch, F. W.) 440–452 (Academic, New York, 1982).
Julius, M. H., Simpson, E. & Herzenberg, L. A. Eur. J. Immun. 3, 645–651 (1973).
Cochet, C., Gill, G. N., Meisenhelder, J., Cooper, J. A. & Hunter, T. J. biol. Chem. 259, 2553–2558 (1984).
Iwashita, S. & Fox, C. F. J. biol. Chem. 259, 2559–2567 (1984).
Davis, R. J. & Czech, M. P. J. biol. Chem. 259, 8545–8551 (1984).
Stadel, J. M. et al. Proc. natn. Acad. Sci. U.S.A. 80, 3173–3177 (1983).
Cantrell, D. A., Davies, A. A. & Crumpton, M. J. Proc. natn. Acad. Sci. U.S.A. 82, 8158–8162 (1985).
May, W. S., Jacobs, S. & Cuatrecasas, P. Proc. natn. Acad. Sci. U.S.A. 81, 2016–2020 (1984).
May, W. S., Sahyoun, N., Jacobs, S., Wolf, M. & Cuatrecasas, P. J. biol. Chem. 260, 9419–9426 (1985).
Klausner, R. D. et al. Proc. natn. Acad. Sci. U.S.A. 81, 3005–3009 (1984).
Laemmli, U. K. Nature 227, 680–685 (1970).
Cleveland, D. W., Fischer, S. G., Kirschner, M. W. & Laemmli, U. K. J. biol. Chem. 252, 1102–1106 (1977).
Adachi, A. et al. J. Virol. 59, 284–292 (1986).
Hoxie, J. et al. J. Immun. 140, 786–795 (1988).
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Fields, A., Bednarik, D., Hess, A. et al. Human immunodeficiency virus induces phosphorylation of its cell surface receptor. Nature 333, 278–280 (1988). https://doi.org/10.1038/333278a0
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DOI: https://doi.org/10.1038/333278a0
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