E box motifs as mediators of proviral latency of human retroviruses.
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.
Terme
Jean-Michel
JM
Institut de Biologia Molecular Barcelona IBMB-CSIC, Parc Cientific de Barcelona, 08028 Barcelona, Spain. jeanmichel.terme@ibmb.csic.es
Calvignac
Sébastien
S
Duc Dodon
Madeleine
M
Gazzolo
Louis
L
Jordan
Albert
A
D024721:E-Box Elements / Q000502:physiology*; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D020079:Terminal Repeat Sequences / Q000235:genetics; D014158:Transcription, Genetic; D017735:Virus Latency