Journal article
Structure and function of a highly conserved HIV-1 LTR downstream regulatory element
Journal of neurovirology, Vol.13, pp.98-98
01 Jan 2007
Abstract
At least one CCAAT enhancer binding protein (C/EBP) site upstream of the TATA box is necessary for human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) activity in cells of the monocyte-macrophage lineage. However, no studies have been performed concerning C/EBP sites downstream (DS) of the start of transcription. TRANSFAC analyses of 100 subtype B LTRs have indicated three potential C/EBP binding sites within the DS LTR. However, EMS analyses demonstrated that only one of the three sites (DS3, +158 to +175) was able to form DNA-protein complex(es) containing C/EBPbeta. Transient transfection studies utilizing the parental HIV-1 LAI-LTR or the LAI-LTR containing a knock-out 9C variant (LTR-DS3-9C, G-to-C change at position 9 of the site) demonstrated loss of binding to this site results in an approximate 50% decrease in basal LTR activity in the TF-1, U-937, and THP-1 monocyte-macrophage cell lines. In addition, C/EBP-induced activation of the LAI-LTR was reduced based on the loss of C/EBP binding to DS3. Interestingly, Tat-mediated transactivation of the LAI-LTR was elevated in the presence of the 9C knockout with co-expression of C/EBPbeta and Tat resulted in an even greater level of transactivation. Tatmediated transactivation of the HIV-1 LAI-LTR was also enhanced in the presence IL-6 with the LAI-DS3-9C knockout. These results suggest that sequence alterations in the highly conserved DS3 element may influence the interaction of Tat with the HIV-1 LTR thereby affecting HIV-1 transcription. This interaction may be a critical element required for HIV-1 transcriptional regulation.
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Details
- Title
- Structure and function of a highly conserved HIV-1 LTR downstream regulatory element
- Creators
- Y LiuM NonnemacherE KilareskiA AlexakiB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.98-98
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170505404721