Document Detail


Identification of a novel glucocorticoid response element within the genome of the human immunodeficiency virus type 1.
MedLine Citation:
PMID:  7684876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown that (HIV-1) replication can be regulated by interaction between glucocorticoid hormones and the viral genome; treatment of acutely infected lymphoid and monocytoid cell lines with cortisol and dexamethasone increased HIV-1 production in culture. The magnitude of this response correlated with glucocorticoid receptor (GR) and GR message in responder and non-responder cell lines. Furthermore, treatment of each of two HIV-infected cell lines with glucocorticoids led to enhancement of HIV-1 gene expression. We have identified a novel intragenic glucocorticoid response element (GRE) within the genome of HIV-1 at position +5002 in the vif open reading frame, as well as a second potential GRE, previously identified by other researchers at position -257 in the HIV-1 negative regulatory element (LTR-NRE). Our data indicate that only the motif at position +5002 represents a true GRE that confers glucocorticoid inducibility to a MMTV-luciferase reporter gene construct. The GRE located at -257 lacked significant functional activity in its native configuration in that it could bind GR but did not transactivate reporter gene constructs. However, this sequence was able to impart glucocorticoid inducibility when inverted or dimerized. These results suggest that as in the case of other retroviruses, HIV-1 has evolved to interface with the GR signal transduction pathway to gain replicative advantage in target cells.
Authors:
H Soudeyns; R Geleziunas; G Shyamala; J Hiscott; M A Wainberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virology     Volume:  194     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-06-25     Completed Date:  1993-06-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  758-68     Citation Subset:  IM; X    
Affiliation:
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Binding, Competitive
Cell Line
Cytosol / metabolism
DNA, Viral / metabolism
Dexamethasone / pharmacology*
Gene Expression Regulation, Viral
Genome, Viral
HIV-1 / drug effects,  genetics*,  growth & development
Humans
Hydrocortisone / pharmacology*
Molecular Sequence Data
RNA, Messenger / metabolism
RNA, Viral / metabolism
RNA-Directed DNA Polymerase / biosynthesis
Receptors, Glucocorticoid / biosynthesis,  drug effects
Regulatory Sequences, Nucleic Acid / genetics*
Sequence Homology, Nucleic Acid
Transcription, Genetic
Virus Replication / drug effects
Chemical
Reg. No./Substance:
0/DNA, Viral; 0/RNA, Messenger; 0/RNA, Viral; 0/Receptors, Glucocorticoid; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; EC 2.7.7.49/RNA-Directed DNA Polymerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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