NDLI: The Nef protein of HIV-1 associates with rafts and primes T cells for activation.

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The Nef protein of HIV-1 associates with rafts and primes T cells for activation.

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The Nef protein of HIV-1 associates with rafts and primes T cells for activation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kiyokawa, E. Wang, J. K. Verdin, E. Trono, D.
Description	Author Affiliation: Wang JK ( Department of Genetics and Microbiology, University of Geneva, CH-1211 Geneva, Switzerland.);
Abstract	The Nef protein is an important virulence factor of primate lentiviruses, yet the mechanisms by which it exerts this influence are imperfectly understood. Here, using an inducible system, we demonstrate that Nef increases IL-2 secretion from T cells stimulated via CD3 or CD28. This effect requires the conservation of the Nef myristoylation signal and SH3-binding proline-based motif. Together with several proteins involved in the initiation and propagation of T cell signaling, Nef associates with membrane microdomains known as rafts. The Nef-mediated superinduction of IL-2 reflects the activation of both NFAT and NFkappaB. Accordingly, Nef also enhances HIV-1 transcription in response to CD3 or CD28 stimulation. Nef-induced IL-2 hyperresponsiveness is also observed in primary CD4 lymphocytes. Overall, these data suggest that Nef acts at the level of rafts to prime T cells for activation. Likely consequences of this effect are the promotion of HIV-1 replication and the facilitation of virus spread.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	CD4-Positive T-Lymphocytes Metabolism Gene Products, Nef Pharmacology HIV-1 Lymphocyte Activation Immunology Nuclear Proteins Antigens, CD DNA-Binding Proteins Gene Expression Regulation, Viral Genes, Reporter Glycolipids HIV Long Terminal Repeat Genetics Interleukin-2 Secretion Jurkat Cells Myristic Acid NF-kappa B NFATC Transcription Factors Promoter Regions, Genetic Signal Transduction Transcription Factors Virus Replication Nef Gene Products, Human Immunodeficiency Virus Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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