title: 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.affiliation: Division of Rheumatology, The Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: Nithianandan
authors.initials: N
authors.lastname: Selliah
authors.forename: Mingce
authors.initials: M
authors.lastname: Zhang
authors.forename: Dennis
authors.initials: D
authors.lastname: DeSimone
authors.forename: Hellen
authors.initials: H
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Brunner
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ittenbach
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.forename: Randy Q
authors.initials: RQ
authors.lastname: Cron
authors.forename: Terri H
authors.initials: TH
authors.lastname: Finkel
mesh_terms: D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D016207:Cytokines; D050799:STAT5 Transcription Factor