title: Impact of viral activators and epigenetic regulators on HIV-1 LTRs containing naturally occurring single nucleotide polymorphisms.
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.
authors: 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.
authors: Sonia
authors: S
authors: Shah
authors: 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.
authors: Vanessa
authors: V
authors: Pirrone
authors: 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.
authors: Aikaterini
authors: 0000-0003-2511-8569
authors: A
authors: Alexaki
authors: 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.
authors: Michael R
authors: MR
authors: Nonnemacher
authors: 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.
authors: Brian
authors: 0000-0002-5211-0936
authors: B
authors: Wigdahl
mesh_terms: D045744:Cell Line, Tumor; D002999:Clone Cells; D044127:Epigenesis, Genetic / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D006877:Hydroxamic Acids; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; C012589:trichostatin A
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