Regulation of HIV -1 gene expression by NF -IL6 in T cells

2000 2000

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Abstract (summary)

Genetic and biochemical studies have shown that human immunodeficiency virus type-1 (HIV-1) transcription is regulated in part by overlapping cis-acting elements in the viral long terminal repeat (LTR). These elements provide binding sites for numerous cellular transcription factors including TFIID, Sp1, NF-κB, NF-IL6, and USF. Previous studies have identified a binding site for NF-IL6 (nucleotides −173 to −165) that overlaps the E box that interacts with USF. DNA-binding studies showed that in Jurkat cells stimulated with lipopolysaccharide (LPS) and phorbol myristate acetate (PMA), the production of the endogenous NF-IL6 was not induced. The absence of endogenous NFIL6 in Jurkat cells provided a suitable system to examine the effect of exogenous NF-IL6 in cells activated with LPS+PMA. The results showed that in stimulated cells, exogenous NF-IL6 upregulated LTR-mediated transcription. However, mutations in the NF-IL6 site did not abolish the effect of NF-IL6 on LTR-mediated gene expression. Several deletion reporter constructs were analyzed to localize the region through which NF-IL6 transactivated the LTR. The results showed that in Jurkat cells only the basal LTR sequences were needed for LTR transactivation by NF-IL6. The basal LTR region also responded moderately to the cellular activation by LPS and PMA in the absence of NF-IL6. The presence of exogenous NF-IL6 elevated this response while the response was down-regulated by another family member, hC/EBPα. Also, exogenous NF-IL6 did not activate gene expression through constructs containing the promoter region of the thymidine kinase gene. Furthermore, exogenous production of several factors (including MyoD, B-ATF, VP16-BATF, and Myc) did not elevate expression through the basal region of the LTR. Thus, the regulatory effects of NF-IL6 on the HIV-1 LTR appear to be unique to this viral promoter.

Indexing (details)

Molecular biology;
0307: Molecular biology
0487: Biochemistry
Identifier / keyword
Pure sciences; Biological sciences; Gene expression; HIV-1; NF-IL6; T cells
Regulation of HIV -1 gene expression by NF -IL6 in T cells
Buckner, Anissa Evans
Number of pages
Publication year
Degree date
School code
DAI-B 62/06, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
0493286489, 9780493286488
Bina, Minou
Purdue University
University location
United States -- Indiana
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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