Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA
| Autor: | Paul Berg, Sylvie Luria, Ian Chambers |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Interleukin 2
Chloramphenicol O-Acetyltransferase Receptor complex Genes Viral Transcription Genetic viruses T-Lymphocytes Receptors Antigen T-Cell Biology Lymphocyte Activation Transfection Jurkat cells Gene Products nef Chloramphenicol acetyltransferase chemistry.chemical_compound Antigen medicine Humans RNA Messenger nef Gene Products Human Immunodeficiency Virus Promoter Regions Genetic Multidisciplinary Ionomycin virus diseases Molecular biology chemistry Gene Expression Regulation HIV-1 Interleukin-2 Tetradecanoylphorbol Acetate Alpha chain medicine.drug Plasmids Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 88(12) |
| ISSN: | 0027-8424 |
| Popis: | Stable transformants of the Jurkat T-cell line have been obtained that express either of two distinct forms of the type 1 human immunodeficiency virus nef gene: the nef-1-encoded protein (Nef-1) contains alanine, glycine, and valine at positions 15, 29, and 33, respectively; the protein specified by nef-2 (Nef-2) has threonine, arginine, and alanine at the corresponding positions. When Jurkat cells or their Nef-2-expressing transformants are treated with phorbol 12-myristate 13-acetate (PMA) plus either phytohemagglutinin (PHA) or antibodies against CD3 epsilon, T-cell receptor beta chain, or CD2, there is a prompt increase in interleukin 2 (IL-2) mRNA and intracellular calcium and in the IL-2 receptor alpha chain on the cell surface. Although cells expressing Nef-1 also induce calcium mobilization and the production of IL-2 receptor alpha chain, the formation of IL-2 mRNA is blocked in response to these stimuli. Moreover, Nef-1-expressing cells transfected with a plasmid in which the IL-2 promoter is fused to the chloramphenicol acetyltransferase (CAT) gene fail to induce CAT following treatment with PMA and PHA. By contrast, the parental and Nef-2-containing cells induce CAT normally. Nef-1-expressing cells can produce IL-2 mRNA in response to a combination of PMA and ionomycin, although much less efficiently than the parental Jurkat cells or Nef-2-expressing cells. These findings, and others described herein, suggest that the virally encoded Nef protein interferes with a signal emanating from the T-cell receptor complex that induces IL-2 gene transcription. |
| Databáze: | OpenAIRE |
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