The gammac-cytokine regulated transcription factor, STAT5, increases HIV-1 production in primary CD4 T cells.

Abstract

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.

• Authors: Nithianandan Selliah, Mingce Zhang, Dennis DeSimone, Hellen Kim, Michael Brunner, Richard F Ittenbach, Hallgeir Rui, Randy Q Cron, Terri H Finkel
• Journal: Virology (Virology) Vol. 344 Issue 2 Pg. 283-91 (Jan 20 2006) ISSN: 0042-6822 [Print] United States
• PMID: 16289657 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• STAT5 Transcription Factor

Topics

• Binding Sites
• CD4-Positive T-Lymphocytes (metabolism, virology)
• Cells, Cultured
• Cytokines (pharmacology)
• HIV Long Terminal Repeat (genetics)
• HIV-1 (physiology)
• Humans
• STAT5 Transcription Factor (metabolism)
• Virus Replication