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Open Access Commentary

E box motifs as mediators of proviral latency of human retroviruses

Jean-Michel Terme1, Sébastien Calvignac2, Madeleine Duc Dodon3*, Louis Gazzolo3 and Albert Jordan1*

Author Affiliations

1 Institut de Biologia Molecular Barcelona IBMB-CSIC, Parc Cientific de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain

2 Université de Lyon, UMR CNRS 5023, Laboratoire d'Ecologie des Hydrosystèmes Fluviaux, Campus de la Doua, 43, Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France

3 INSERM U758 Virologie Humaine, IFR 128 Biosciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 4, Allée d'Italie, 69364 Lyon Cedex 07, France

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Retrovirology 2009, 6:81  doi:10.1186/1742-4690-6-81

Published: 16 September 2009

Abstract

The palindromic sequence motifs (CANNTG) known as E boxes are considered as binding sites for the basic helix-loop-helix (bHLH) class of DNA-binding proteins. Their presence has been reported in the long terminal repeats (LTR) of the HIV-1 and HTLV-1 proviruses. Their close proximity with the TATA region of both LTRs indicates that the bHLH proteins may act as important regulators of the function of proviral transcription. Indeed, observations on HIV-1 and recent results on HTLV-1 underline that these E boxes may be critically involved in the regulation of the proviral transcription of these human retroviruses. Indeed, of the two E boxes flanking the TATA sequences of the HIV-1 provirus, the 3' E box has been implicated in the transcriptional inhibition of viral gene expression. Such a role might also be played by the unique 5' E box present in the HTLV-1 LTR. In both cases, the expression of tissue-specfic bHLH proteins, like TAL1 might counteract the inhibitory effect exerted by E box proteins, thereby increasing proviral transcription. Finally, a phylogenetic study encompassing several subtypes of these two human retroviruses underlines that these E box motifs have recently appeared in the proviral LTRs and may be considered as potential mediators in the establishment of proviral latency.