Abstract
A DECLINE in the T-cell population usually marks the onset of progressive immunological disease in individuals infected with the human immunodeficiency virus (HIV). Because CD4+ cells help to coordinate efficient immune responses, some of the defects in the immune function in advanced cases of AIDS may be explained by the disappearance of these cells. Therefore, an understanding of the mechanisms used by HIV to induce the reduction of CD4+ cells is important. Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4. In all cases we find that cell-surface CD4 expression is inversely related to nef expression. However, nef does not alter steady-state levels of CD4 RNA or CD4 protein. Also, nef can downregulate a CD4 triple mutant (Ser → Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
185,98 € per year
only 3,65 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dalgleish, A. G. et al Nature 312, 763–767 (1985).
Haseltine, W. A., Terwilliger, D. F., Rosen, C. A. & Sodroski, J. G. in Retrovirus Biology and Human Disease, (eds Gallo, R. C. & Wong-Staal, F.) (Dekker, New York, 1990).
Pavlakis, G. M. & Felberg, B. K. New Biol. 2, 20–31 (1990).
Ratner, L. et al. Nature 313, 277–284 (1985).
Franchini, G., Robert-Guroff, M., Ghrayeb, J., Chang, N. T. & Wong-Staal, F. Virology 155, 593–599 (1986).
Ahmad, N. & Venkatesan, S. Science 241, 1481–1485 (1988).
Kim, S., Ikeuchi, K., Byrn, R., Groopman, J. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 86, 9544–9548 (1989).
Hammes, S., Dixon, E., Malim, M., Cullen, B. & Greene, W. C. Proc. natn. Acad. Sci. U.S.A. 86, 9549–9553 (1989).
Guy, B. et al. Nature 330, 266–269 (1987).
Cheng-Mayer, C., Iannello, P., Shaw, K., Luciw, P. A. & Levy, J. A. Science 246, 1629–1632 (1989).
Miller, A. D. & Rosman, G. Biotechniques 7, 980–990 (1989).
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., Mochizoki, D. Y. & Gallis, B. J. biol. Chem. 261, 16210–16214 (1986).
Shin, J., Doyle, C., Yang, Z., Kappes, D. & Strominger, J. L. EMBO J. 9, 425–434 (1990).
Fauci, A. S. Science 239, 617–622 (1988).
Gallo, R. C. J. acq. Immun. Defic. Synd. 3, 380–389 (1990).
Temin, H. M., Keshet, E. & Weller, S. K. in Cold Spring Harb. Symp. quant. Biol. Vol. XLIV 773–778 (Cold Spring Harbor Laboratory, New York, 1980).
Weller, S. K., Joy, A. E. & Temin, H. M. J. Virol. 33, 494–506 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Garcia, J., Miller, A. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 350, 508–511 (1991). https://doi.org/10.1038/350508a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/350508a0