FOXP3 inhibits HIV-1 infection of CD4 T-cells via inhibition of LTR transcriptional activity

Academic Article


  • 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 NFκB/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 NFκB binding sites. These data suggest that resistance of Tregs to HIV-1 infection is due to inhibition of HIV-1 LTR transcription by FOXP3. © 2008 Elsevier Inc. All rights reserved.
  • Published In

  • Virology  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 27661715
  • Author List

  • Selliah N; Zhang M; White S; Zoltick P; Sawaya BE; Finkel TH; Cron RQ
  • Start Page

  • 161
  • End Page

  • 167
  • Volume

  • 381
  • Issue

  • 2