Document Detail


Regulation of SIV mac 239 basal long terminal repeat activity and viral replication in macrophages: functional roles of two CCAAT/enhancer-binding protein beta sites in activation and interferon beta-mediated suppression.
MedLine Citation:
PMID:  19933495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CCAAT/enhancer-binding protein (C/EBP) beta and C/EBP sites in the HIV-1 long terminal repeat (LTR) are crucial for HIV-1 replication in monocyte/macrophages and for the ability of interferon beta (IFN beta) to inhibit ongoing active HIV replication in these cells. This IFN beta-mediated down-regulation involves induction of the truncated, dominant-negative isoform of C/EBP beta referred to as liver-enriched transcriptional inhibitory protein (LIP). Although binding of the C/EBP beta isoform to C/EBP sites in the simian immunodeficiency virus (SIV) LTR has previously been examined, the importance of these sites in core promoter-mediated transcription, virus replication, IFN beta-mediated regulation, and the relative binding of the two isoforms (C/EBP beta and LIP) has not been investigated. Here, we specifically examine two C/EBP sites, JC1 (-100 bp) and DS1 (+134 bp), located within the minimal region of the SIV LTR, required for core promoter-mediated transcription and virus replication in macrophages. Our studies revealed that the JC1 but not DS1 C/EBP site is important for basal level transcription, whereas the DS1 C/EBP site is imperative for productive virus replication in primary macrophages. In contrast, either JC1 or DS1 C/EBP site is sufficient to mediate IFN beta-induced down-regulation of SIV LTR activity and virus replication in these cells. We also characterized the differential binding properties of C/EBP beta and LIP to the JC1 and DS1 sites. In conjunction with previous studies from our laboratory, we demonstrate the importance of these sites in virus gene expression, and we propose a model for their role in establishing latency and persistence in macrophages in the brain.
Authors:
Shruthi Ravimohan; Lucio Gama; Sheila A Barber; Janice E Clements
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-11-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-18     Completed Date:  2010-02-22     Revised Date:  2011-07-20    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2258-73     Citation Subset:  IM    
Affiliation:
McKusick-Nathans Institute of Genetic Medicine and Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CCAAT-Enhancer-Binding Protein-beta / metabolism*
Cell Line
Encephalitis, Viral / immunology,  virology
Humans
Interferon-beta / metabolism*
Kidney / cytology
Luciferases / genetics
Macaca mulatta
Macrophages / cytology,  virology*
Proliferating Cell Nuclear Antigen / metabolism
Promoter Regions, Genetic / physiology
Simian immunodeficiency virus / genetics,  growth & development*
Terminal Repeat Sequences / physiology
Transcriptional Activation / physiology
Transfection
Virus Latency / physiology
Virus Replication / physiology*
Grant Support
ID/Acronym/Agency:
HL75840/HL/NHLBI NIH HHS; MH070306/MH/NIMH NIH HHS; NS047984/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-beta; 0/Proliferating Cell Nuclear Antigen; 0/p27 antigen; 77238-31-4/Interferon-beta; EC 1.13.12.-/Luciferases
Comments/Corrections

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