Journal article
Transcriptional competency of HIV-1 LTR genetic variants in an integrated chromatin-based environment
Journal of neurovirology, Vol.12
01 May 2006
Abstract
Human immunodeficiency virus type 1 (HIV-1) gene expression is driven by the long terminal repeat (LTR), which has a variety of binding sites for the interaction with multiple host and viral factors, including members of the CCAAT/enhancer binding protein (C/EBP) and Sp transcription factor families. We have previously identified specific nucleotide sequence configurations within C/EBP site I (C to T change at position 3; 3T) and Sp site III (C to T change at position 5; 5T) which correlate with increased severity of HIV-1 disease and HIV-1-associated dementia. As one approach to begin exploring the LTR phenotype associated with these genotypic changes with respect to LTR-directed transcription from an integrated chromatin-based microenvironment, a series of stably transfected cell lines have been developed utilizing bone marrow progenitor (TF-1), T (Jurkat), and monocytic cell lines (U-937). To this end, macrophage-, T cell-, and dual-tropic LTRs were coupled to the gene encoding green fluorescent protein (GFP). The resulting HIV-1 LTR GFP stably expressing cell lines were examined under basal, and chemical or cytokine activation, as well as in the presence of HIV-1 Tat. The results demonstrate that the cell type within which these integrated LTRs were expressed produced different expression profiles. In TF-1 cells the 3T/5T-containing LTR drives transcription in all cells but with a lower expressing phenotype, however it can be induced to similar levels as the parental LTR, following stimulation and/or in the presence of Tat. In addition, the backbone, within which this sequence configuration is incorporated, also plays a role in the resulting phenotype. Future studies will examine the impact of specific LTR sequence variation on viral gene expression both in primary cells as well as in viral replication studies.
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Details
- Title
- Transcriptional competency of HIV-1 LTR genetic variants in an integrated chromatin-based environment
- Creators
- A AlexakiM NonnemacherE KilareskiB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170601204721