Impact of Viral Activators and Epigenetic Regulators on HIV-1 LTRs Containing Naturally Occurring Single Nucleotide PolymorphismsReport as inadecuate




Impact of Viral Activators and Epigenetic Regulators on HIV-1 LTRs Containing Naturally Occurring Single Nucleotide Polymorphisms - Download this document for free, or read online. Document in PDF available to download.

BioMed Research International - Volume 2015 2015, Article ID 320642, 14 pages -

Research Article

Department of Microbiology and Immunology, Drexel University College of Medicine School of Medicine, 245 N. 15th Street, MS1013A, Rm 18301, Philadelphia, PA 19102, USA

Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine School of Medicine, Philadelphia, PA 19102, USA

Received 15 May 2014; Revised 29 September 2014; Accepted 14 October 2014

Academic Editor: Venkat Yedavalli

Copyright © 2015 Sonia Shah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Author: Sonia Shah, Vanessa Pirrone, Aikaterini Alexaki, Michael R. Nonnemacher, and Brian Wigdahl

Source: https://www.hindawi.com/



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