Structural and functional studies of CCAAT/enhancer binding sites within the human immunodeficiency virus type 1 subtype C LTR

• Published in: Biomedicine & pharmacotherapy 2010-12, Vol.64 (10), p.672-680
• Main Authors: Liu, Yujie, Nonnemacher, Michael R, Stauff, Devin L, Li, Luna, Banerjee, Anupam, Irish, Bryan, Kilareski, Evelyn, Rajagopalan, Nirmala, Suchitra, Joyce B, Khan, Zafar K, Ranga, Udaykumar, Wigdahl, Brian
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites; Biological and medical sciences; C/EBPβ; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Line; Gene Expression Regulation, Viral; HIV Long Terminal Repeat; HIV-1; HIV-1 - genetics; HIV-1 - metabolism; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Internal Medicine; LTR; Medical Education; Medical sciences; Molecular Sequence Data; Monocyte-Macrophage Precursor Cells - physiology; Monocyte-Macrophage Precursor Cells - virology; Pharmacology. Drug treatments; Protein Binding; Sequence Alignment; Sequence Analysis, DNA; Subtype C; T-Lymphocytes - physiology; T-Lymphocytes - virology; tat Gene Products, Human Immunodeficiency Virus - genetics; TATA Box - genetics; Transcription; Transcription, Genetic; Transcriptional Activation; U937 Cells; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Replication
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2010.09.007

Abstract Human immunodeficiency virus type 1 (HIV-1) subtype C, which is most predominant in sub-Saharan Africa as well as in Asia and India, is the most prevalent subtype worldwide. A large number of transcription factor families have been shown to be involved in regulating HIV-1 gene expression in T lymphocytes and cells of the monocyte-macrophage lineage. Among these, proteins of the CCAAT/enhancer binding protein (C/EBP) family are of particular importance in regulating HIV-1 gene expression within cells of the monocytic lineage during the course of hematologic development and cellular activation. Few studies have examined the role of C/EBPs in long terminal repeat (LTR)-directed viral gene expression of HIV-1 subtypes other than subtype B. Within subtype B viruses, two functional C/EBP sites located upstream of the TATA box are required for efficient viral replication in cells of the monocyte-macrophage lineage. We report the identification of three putative subtype C C/EBP sites, upstream site 1 and 2 (C-US1 and C-US2) and downstream site 1 (C-DS1). C-US1 and C-DS1 were shown to form specific DNA-protein complexes with members of the C/EBP family (C/EBPα, β, and δ). Functionally, within the U-937 monocytic cell line, subtype B and C LTRs were shown to be equally responsive to C/EBPβ-2, although the basal activity of subtype C LTRs appeared to be higher. Furthermore, the synergistic interaction between C/EBPβ-2 and Tat with the subtype C LTR was also observed in U-937 cells as previously demonstrated with the subtype B LTR.