The γc-cytokine regulated transcription factor, STAT5, increases HIV-1 production in primary CD4 T cells
| Autor: | Mingce Zhang, Hellen Kim, Hallgeir Rui, Michael Brunner, Terri H. Finkel, Dennis DeSimone, Randy Q. Cron, Nithianandan Selliah, Richard F. Ittenbach |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
LTR medicine.medical_treatment Signal transduction Biology Virus Replication 03 medical and health sciences Transcription (biology) Virology STAT5 Transcription Factor medicine Humans Transcription factor STAT4 Cells Cultured STAT5 HIV Long Terminal Repeat 030304 developmental biology 0303 health sciences Binding Sites 030306 microbiology Janus kinase 3 HIV virus diseases Long terminal repeat Gene regulation 3. Good health Cytokine HIV-1 STAT protein biology.protein Cytokines |
| Zdroj: | Virology. 344:283-291 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2005.09.063 |
| Popis: | Although HIV-1 (HIV) replicates poorly in non-dividing CD4 lymphocytes, resting T cells contribute to the latent reservoir. The gammac-related cytokines reverse this block to HIV infection; however, the molecular mechanisms controlling this process are not understood. We asked whether the gammac-cytokine regulated transcription factor, signal transducer and activator of transcription 5 (STAT5), activates HIV transcription. We identified three regions in the long terminal repeat (LTR) as close matches to the STAT5 consensus-binding site and show that STAT5 binds the LTR during HIV infection. Expression of Janus kinase 3 (JAK3) or STAT5 in primary human CD4 T cells activated LTR transcription, while transactivation-incompetent dominant-negative STAT5 inhibited JAK3-induced LTR activity and infection of activated HIV-producing CD4 T-cells. In addition, overexpression of STAT5 increased virus production in unstimulated primary T cells - both the number of p24+ cells and their level of p24 production - suggesting that STAT5 promotes a permissive state for HIV infection. These data may have implications for regulation of latency and therapeutic strategies for control of HIV disease. |
| Databáze: | OpenAIRE |
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