Structural and functional studies of CCAAT/enhancer binding sites within the human immunodeficiency virus type 1 subtype C LTR.
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.
Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA.
Yujie
Y
Liu
Michael R
MR
Nonnemacher
Devin L
DL
Stauff
Luna
L
Li
Anupam
A
Banerjee
Bryan
B
Irish
Evelyn
E
Kilareski
Nirmala
N
Rajagopalan
Joyce B
JB
Suchitra
Zafar K
ZK
Khan
Udaykumar
U
Ranga
Brian
B
Wigdahl
D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D055017:Monocyte-Macrophage Precursor Cells / Q000502:physiology / Q000821:virology; D011485:Protein Binding; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020298:U937 Cells; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus