Human T-cell lymphotropic virus type 1 p12I enhances interleukin-2 production during T-cell activation
| Autor: | Michael Dale Lairmore, Gerold Feuer, Adam Tripp, Bindhu Michael, Kathleen Boris-Lawrie, Wei Ding, Amrithraj M. Nair, Seung Jae Kim |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Interleukin 2
viruses T cell T-Lymphocytes Immunology Amino Acid Motifs Receptors Antigen T-Cell Biology Endoplasmic Reticulum Lymphocyte Activation Microbiology Jurkat cells Viral vector Cell Line CD28 Antigens Virology medicine Humans Viral Regulatory and Accessory Proteins Human T cell lymphotropic virus type 1 Binding Sites NFATC Transcription Factors T-cell receptor Nuclear Proteins NFAT Oncogene Proteins Viral Molecular biology Virus-Cell Interactions DNA-Binding Proteins medicine.anatomical_structure Insect Science Interleukin-2 Tetradecanoylphorbol Acetate Calcium medicine.drug Transcription Factors |
| Zdroj: | Journal of virology. 77(20) |
| ISSN: | 0022-538X |
| Popis: | Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and a variety of lymphoproliferative disorders. The early virus-cell interactions that determine a productive infection remain unclear. However, it is well recognized that T-cell activation is required for effective retroviral integration into the host cell genome and subsequent viral replication. The HTLV-1 pX open reading frame I encoding protein, p12 I , is critical for the virus to establish persistent infection in vivo and for infection in quiescent primary lymphocytes in vitro. p12 I localizes in the endoplasmic reticulum (ER) and cis-Golgi apparatus, increases intracellular calcium and activates nuclear factor of activated T cells (NFAT)-mediated transcription. To clarify the function of p12 I , we tested the production of IL-2 from Jurkat T cells and peripheral blood mononuclear cells (PBMC) expressing p12 I . Lentiviral vector expressed p12 I in Jurkat T cells enhanced interleukin-2 (IL-2) production in a calcium pathway-dependent manner during T-cell receptor (TCR) stimulation. Expression of p12 I also induced higher NFAT-mediated reporter gene activities during TCR stimulation in Jurkat T cells. In contrast, p12 expression in PBMC elicited increased IL-2 production in the presence of phorbal ester stimulation, but not during TCR stimulation. Finally, the requirement of ER localization for p12 I -mediated NFAT activation was demonstrated and two positive regions and two negative regions in p12 I were identified for the activation of this transcription factor by using p12 I truncation mutants. These results are the first to indicate that HTLV-1, an etiologic agent associated with lymphoproliferative diseases, uses a conserved accessory protein to induce T-cell activation, an antecedent to efficient viral infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|