Human T Lymphotropic Virus Type 1 Accessory Protein p12IModulates Calcium-Mediated Cellular Gene Expression and Enhances p300 Expression in T Lymphocytes
| Autor: | Kathleen Boris-Lawrie, Michael Dale Lairmore, Bindhu Michael, Hajime Hiraragi, Soledad Fernandez, Amrithraj M. Nair, Gerold Feuer |
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| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic T-Lymphocytes T cell Immunology Apoptosis Biology Jurkat cells Article TCIRG1 Jurkat Cells Interleukin 21 hemic and lymphatic diseases Virology medicine Humans Cytotoxic T cell Viral Regulatory and Accessory Proteins RNA Messenger Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction ZAP70 Nuclear Proteins CD28 Oncogene Proteins Viral T lymphocyte Molecular biology Infectious Diseases medicine.anatomical_structure Gene Expression Regulation Trans-Activators Cell Division Signal Transduction Transcription Factors |
| Zdroj: | AIDS Research and Human Retroviruses. 21:273-284 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2005.21.273 |
| Popis: | Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia/lymphoma (ATLL), an aggressive CD4+ T lymphocyte malignancy. Activation of T lymphocytes is required for effective retroviral integration into the host cell genome and subsequent viral replication, but the molecular mechanisms involved in HTLV-1-mediated T cell activation remain unclear. HTLV-1 encodes various accessory proteins such as p12I, which has been demonstrated to be critical for HTLV-1 infectivity in vivo in rabbits and in vitro in quiescent primary human T lymphocytes. This hydrophobic protein localizes in the endoplasmic reticulum, increases intracellular calcium, and activates nuclear factor of activated T cell-mediated transcription. To further elucidate the role of p12I in regulation of cellular gene expression, we performed gene array analysis on stable p12I-expressing Jurkat T cells, using Affymetrix U133A arrays. Our data indicate that p12I altered the expression of genes associated with a network of interrelated pathways including T cell signaling, cell proliferation, and apoptosis. Expression of several calcium-regulated genes was found to be altered by p12I, consistent with known properties of the viral protein. Gene array findings were confirmed by semiquantitative RT-PCR in Jurkat T cells and primary CD4+ T lymphocytes. Furthermore, dose-dependent expression of p12I in Jurkat T cells resulted in significant increases in p300 and p300-dependent transcription. This is the first report of a viral protein influencing the transcription of p300, a rate-limiting coadapter critical in HTLV-1-mediated T cell activation. Collectively, our data strongly indicate that HTLV-1 p12I modulates cellular gene expression patterns to hasten the activation of T lymphocytes and thereby promote efficient viral infection. |
| Databáze: | OpenAIRE |
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