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

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-cyt...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2006-01, Vol.344 (2), p.283-291
Main Authors: Selliah, Nithianandan, Zhang, Mingce, DeSimone, Dennis, Kim, Hellen, Brunner, Michael, Ittenbach, Richard F, Rui, Hallgeir, Cron, Randy Q, Finkel, Terri H
Format: Article
Language:English
Subjects:
Binding Sites
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - virology
Cells, Cultured
Cytokines - pharmacology
HIV Long Terminal Repeat - genetics
HIV-1 - physiology
Humans
STAT5 Transcription Factor - metabolism
Virus Replication
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Summary: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.
ISSN:0042-6822
1096-0341