Abstract
Gene expression profiling was used to explore the role of Nef in HIV. Nef induces a transcriptional program in T cells that is 97% identical to that of anti-CD3 T cell activation. This program is inhibited in the presence of cyclosporin. A requirement for TCR zeta and ZAP-70 is demonstrated for formation of the complete profile. Among eight factors particular to the anti-CD3 activation profile are IL16 and YY1, negative regulators of HIV transcription. In contrast, Nef exclusively upregulates factors positively regulating HIV, including Tat-SF1, U1 SNRNP, and IRF-2. New genes associated with Nef include CDK9, the induction of which enhances Tat function. Thus, Nef acts as a master switch early in the viral life cycle, forcing an environment conducive to dynamic viral production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclin-Dependent Kinase 9
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Cyclin-Dependent Kinases / metabolism
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Cyclosporine / pharmacology
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Gene Expression Profiling*
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Gene Products, nef / immunology*
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HIV-1 / immunology*
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HIV-1 / pathogenicity
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Humans
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Immunosuppressive Agents / pharmacology
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Jurkat Cells
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Lymphocyte Activation / immunology*
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Membrane Proteins / immunology
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Protein-Tyrosine Kinases / immunology
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Receptor-CD3 Complex, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction / immunology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / virology
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Transcription, Genetic*
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Virulence
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ZAP-70 Protein-Tyrosine Kinase
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nef Gene Products, Human Immunodeficiency Virus
Substances
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Gene Products, nef
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Immunosuppressive Agents
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Membrane Proteins
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Receptor-CD3 Complex, Antigen, T-Cell
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Receptors, Antigen, T-Cell
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antigen T cell receptor, zeta chain
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nef Gene Products, Human Immunodeficiency Virus
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Cyclosporine
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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CDK9 protein, human
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Cyclin-Dependent Kinase 9
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Cyclin-Dependent Kinases