HIV Nef-mediated Cellular Phenotypes Are Differentially Expressed as a Function of Intracellular NEF Concentrations

Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-08, Vol.276 (35), p.32763-32770
Main Authors: Liu, Xunxian, Schrager, Jeffrey A., Lange, G. David, Marsh, Jon W.
Format: Article
Language:English
Subjects:
CD4 antigen
CD4 Antigens - genetics
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Cell Line
Gene Expression Regulation
Gene Expression Regulation, Viral
Gene Products, nef - genetics
Gene Products, nef - metabolism
Genes, MHC Class I
Genes, Reporter
Green Fluorescent Proteins
HIV-1 - genetics
HIV-1 - physiology
HLA-A Antigens - genetics
Human immunodeficiency virus
Humans
Jurkat Cells
Luminescent Proteins - genetics
Lymphocyte Activation
nef Gene Products, Human Immunodeficiency Virus
nef protein
Recombinant Fusion Proteins - metabolism
Simian Immunodeficiency Virus - genetics
T-Lymphocytes - immunology
T-Lymphocytes - virology
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Summary:Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and at times opposing activities has been unclear. Through direct measurements of Nef and the Nef-GFP fusion protein, we find that these events are mediated by different Nef concentrations. Relative to the intracellular concentration that down-modulates surface CD4, an order of magnitude increase in Nef-GFP expression is required for a comparable modulation of major histocompatibility complex class I, and a further 3-fold increase is necessary to suppress T cell activation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M101025200