Serine phosphorylation-independent downregulation of cell-surface CD4 by nef (original) (raw)
- Letter
- Published: 11 April 1991
Nature volume 350, pages 508–511 (1991)Cite this article
- 979 Accesses
- 717 Citations
- 9 Altmetric
- Metrics details
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
$199.00 per year
only $3.90 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
Additional access options:
Similar content being viewed by others
References
- Dalgleish, A. G. et al Nature 312, 763–767 (1985).
Article ADS CAS Google Scholar - 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).
Google Scholar - Pavlakis, G. M. & Felberg, B. K. New Biol. 2, 20–31 (1990).
CAS PubMed Google Scholar - Ratner, L. et al. Nature 313, 277–284 (1985).
Article ADS CAS PubMed Google Scholar - Franchini, G., Robert-Guroff, M., Ghrayeb, J., Chang, N. T. & Wong-Staal, F. Virology 155, 593–599 (1986).
Article CAS PubMed Google Scholar - Ahmad, N. & Venkatesan, S. Science 241, 1481–1485 (1988).
Article ADS CAS PubMed Google Scholar - Kim, S., Ikeuchi, K., Byrn, R., Groopman, J. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 86, 9544–9548 (1989).
Article ADS CAS Google Scholar - Hammes, S., Dixon, E., Malim, M., Cullen, B. & Greene, W. C. Proc. natn. Acad. Sci. U.S.A. 86, 9549–9553 (1989).
Article ADS CAS Google Scholar - Guy, B. et al. Nature 330, 266–269 (1987).
Article ADS CAS PubMed Google Scholar - Cheng-Mayer, C., Iannello, P., Shaw, K., Luciw, P. A. & Levy, J. A. Science 246, 1629–1632 (1989).
Article ADS CAS PubMed Google Scholar - Miller, A. D. & Rosman, G. Biotechniques 7, 980–990 (1989).
CAS PubMed PubMed Central Google Scholar - Hoxie, J. A., Matthews, D. M., Callahan, K. J., Cassel, D. L. & Cooper, R. A. J. Immun. 137, 1194–1201 (1986).
CAS PubMed Google Scholar - Acres, R. B., Conlon, P. J., Mochizoki, D. Y. & Gallis, B. J. biol. Chem. 261, 16210–16214 (1986).
CAS PubMed Google Scholar - Shin, J., Doyle, C., Yang, Z., Kappes, D. & Strominger, J. L. EMBO J. 9, 425–434 (1990).
Article CAS PubMed PubMed Central Google Scholar - Fauci, A. S. Science 239, 617–622 (1988).
Article ADS CAS PubMed Google Scholar - Gallo, R. C. J. acq. Immun. Defic. Synd. 3, 380–389 (1990).
CAS Google Scholar - 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).
Google Scholar - Weller, S. K., Joy, A. E. & Temin, H. M. J. Virol. 33, 494–506 (1980).
CAS PubMed PubMed Central Google Scholar
Author information
Authors and Affiliations
- Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98104, USA
J. Victor Garcia & A. Dusty Miller
Authors
- J. Victor Garcia
You can also search for this author inPubMed Google Scholar - A. Dusty Miller
You can also search for this author inPubMed Google Scholar
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: 21 December 1990
- Accepted: 11 February 1991
- Issue Date: 11 April 1991
- DOI: https://doi.org/10.1038/350508a0