Abstract/Details

Regulation of <i>NF-IL6</i> and HIV-1 expression


1999 1999

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Abstract (summary)

The research focused on the regulation of HIV-1 Long Terminal Repeat (LTR) and human Nuclear Factor for Interleukin 6 (NF-IL6) gene in activated U937 cells. The U937 cells represent human monocytes that differentiate to macrophages upon stimulation with Lipopolysaccharide (LPS) and Phorbol 12-Myristate-13-Acetate (PMA). It is thought that LPS might activate HIV-1 viral production in AIDS patients suffering from bacterial infection. DNA binding assays showed that stimulation of U937 cells with LPS+PMA induced interactions of NF-IL6 and NF-κB with the LTR. The assays further revealed that Sp1, Sp3, and Sp4 interacted with the Sp1 sites in the LTR. These interactions changed as a function of stimulation time while interactions of USF-1/USF-2 with the E-box remained relatively constant. The results of functional assays indicated that several individual factor-binding sites contributed to elevated levels of the LTR activity during cellular stimulation. However, multiple sites in the LTR were necessary for full-scale upregulation of transcription during LPS+PMA stimulation. The results of titration experiments, using a synthetic C/EBP-related peptide as decoy, further implied that in stimulated cells, both site-dependent and -independent pathways were involved in the regulation of HIV-1 gene expression by NF-IL6. To examine whether and how regulation of the NF-IL6 gene is correlated to the activation of LTR by LPS+PMA stimulation, the immediate 5 end of the gene (1.2 kb) was sequenced and subsequently analyzed in biochemical and functional assays. Oligo-scanning analysis identified eleven regions that interacted with nuclear proteins including Sp1 and Sp3, NF-κB and EGR-1. The results of functional analysis further revealed that the NF-IL6 gene was subject to both positive and negative controls, both before and after cellular stimulation with LPS+PMA.

Indexing (details)


Subject
Biochemistry;
Molecular biology
Classification
0487: Biochemistry
0307: Molecular biology
Identifier / keyword
Pure sciences; Biological sciences; HIV-1; Immune deficiency; Lipopolysaccharides; Long terminal repeat; NF-IL6; Phorbol 12-myristate-13 acetate
Title
Regulation of <i>NF-IL6</i> and HIV-1 expression
Author
Yang, Yingmei
Number of pages
280
Publication year
1999
Degree date
1999
School code
0183
Source
DAI-B 62/06, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0493285563, 9780493285566
Advisor
Bina, Minou
University/institution
Purdue University
University location
United States -- Indiana
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3017714
ProQuest document ID
276316975
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/276316975/abstract
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