title: FOXP3 inhibits HIV-1 infection of CD4 T-cells via inhibition of LTR transcriptional activity.
abstract: FOXP3 is a necessary transcription factor for the development and function of CD4+ regulatory T-cells (Tregs). The role of Tregs in HIV-1 infection remains unclear. Here, we show that expression of FOXP3 in primary human CD4 T-cells significantly inhibits HIV-1 infection. Since FOXP3 inhibits NFAT activity, and NFAT proteins contribute to HIV-1 transcription, we explore a transcriptional repressive function of HIV-1 LTR by FOXP3. Over-expression of FOXP3 in primary CD4 T-cells inhibits wild-type HIV-1 LTR reporter activity, and truncation mutants demonstrate that repression of the LTR by FOXP3 requires the dual proximal NF kappaB/NFAT binding sites. Interestingly, FOXP3 decreases binding of NFAT2 to the HIV-1 LTR in vivo. Furthermore, FOXP3 does not inhibit infection of HIV-1 NL4-3 which is mutated to disrupt transcription factor binding at either proximal NFAT or NF kappaB binding sites. These data suggest that resistance of Tregs to HIV-1 infection is due to inhibition of HIV-1 LTR transcription by FOXP3.
authors.affiliation: Division of Rheumatology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Nithianandan
authors.initials: N
authors.lastname: Selliah
authors.forename: Mingce
authors.initials: M
authors.lastname: Zhang
authors.forename: Sara
authors.initials: S
authors.lastname: White
authors.forename: Philip
authors.initials: P
authors.lastname: Zoltick
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
authors.forename: Terri H
authors.initials: TH
authors.lastname: Finkel
authors.forename: Randy Q
authors.initials: RQ
authors.lastname: Cron
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse