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Impact of viral activators and epigenetic regulators on HIV-1 LTRs containing naturally occurring single nucleotide polymorphisms
Journal article   Open access   Peer reviewed

Impact of viral activators and epigenetic regulators on HIV-1 LTRs containing naturally occurring single nucleotide polymorphisms

Sonia Shah, Vanessa Pirrone, Aikaterini Alexaki, Michael R Nonnemacher and Brian Wigdahl
BioMed research international, v 2015, 320642
2015
PMID: 25629043
url
https://doi.org/10.1155/2015/320642View
Published, Version of Record (VoR) Open

Abstract

Hematopoietic Stem Cells - drug effects Green Fluorescent Proteins - metabolism Transcription, Genetic - drug effects Gene Expression Regulation, Viral - drug effects Interleukin-1beta - pharmacology HIV-1 - drug effects Humans Transcriptional Activation - drug effects HIV Long Terminal Repeat - genetics HIV-1 - genetics Tumor Necrosis Factor-alpha - pharmacology Phenotype Transfection Hematopoietic Stem Cells - cytology Cell Line, Tumor Polymorphism, Single Nucleotide - genetics Clone Cells Epigenesis, Genetic - drug effects HIV Long Terminal Repeat - drug effects Hydroxamic Acids - pharmacology
Following human immunodeficiency virus type 1 (HIV-1) integration into host cell DNA, the viral promoter can become transcriptionally silent in the absence of appropriate signals and factors. HIV-1 gene expression is dependent on regulatory elements contained within the long terminal repeat (LTR) that drive the synthesis of viral RNAs and proteins through interaction with multiple host and viral factors. Previous studies identified single nucleotide polymorphisms (SNPs) within CCAAT/enhancer binding protein (C/EBP) site I and Sp site III (3T, C-to-T change at position 3, and 5T, C-to-T change at position 5 of the binding site, respectively, when compared to the consensus B sequence) that are low affinity binding sites and correlate with more advanced stages of HIV-1 disease. Stably transfected cell lines containing the wild type, 3T, 5T, and 3T5T LTRs were developed utilizing bone marrow progenitor, T, and monocytic cell lines to explore the LTR phenotypes associated with these genotypic changes from an integrated chromatin-based microenvironment. Results suggest that in nonexpressing cell clones LTR-driven gene expression occurs in a SNP-specific manner in response to LTR activation or treatment with trichostatin A treatment, indicating a possible cell type and SNP-specific mechanism behind the epigenetic control of LTR activation.

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Web of Science research areas
Biotechnology & Applied Microbiology
Medicine, Research & Experimental
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