Identification of binding sites for members of the CCAAT/enhancer binding protein transcription factor family in the simian immunodeficiency virus long terminal repeat.
Members of the CCAAT/enhancer binding protein (C/EBP) transcription factor family are necessary for human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) activity and viral replication in cells of monocyte/macrophage lineage. The integral roles that HIV-1-infected monocytes and macrophages play in the development and progression of HIV-1-associated disease in the immune and central nervous systems underscore the importance of the C/EBP transcription factor family within the context of regulating HIV-1 gene expression. Although there are considerable similarities between HIV-1 and simian immunodeficiency virus (SIV), including viral-induced immunopathogenesis and neurologic dysfunction, infection of CD4(+) T cells and cells of monocyte/macrophage origin, and LTR structure/function, the involvement of C/EBP factors in regulating SIV transcription has not been previously demonstrated. Analyses of the SIV(mac)239 LTR sequence indicated the presence of five putative C/EBP binding sites within the LTR. Electrophoretic mobility shift (EMS) analyses demonstrated that four of the five sites within the SIV LTR were able to bind C/EBP factors (alpha and beta) and compete for DNA-protein complexes formed by the HIV-1 C/EBP site located adjacent to the promoter-distal NF-kappaB site. DNase I protection assays indicated that purified C/EBPbeta specifically was able to occupy each of the four binding sites. These studies suggest that C/EBP factors may also have important roles in the regulation of SIV gene expression and replication, and that these factors and signal transduction pathways that regulate their activity may impact SIV-associated pathogenesis.
Nonnemacher
Michael R
MR
Department of Microbiology and Immunology (H107), The Pennsylvania State University, College of Medicine, 500 University Drive, P.O. Box 850, Hershey, PA 17033, USA.
Hogan
Tricia H
TH
Quiterio
Shane
S
Wigdahl
Brian
B
Henderson
Andrew
A
Krebs
Fred C
FC
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D006801:Humans; D011485:Protein Binding; D017422:Sequence Analysis, DNA / Q000379:methods; D012689:Sequence Homology, Nucleic Acid; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D020079:Terminal Repeat Sequences / Q000235:genetics*; D020298:U937 Cells
D022762:CCAAT-Enhancer-Binding Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins