Document Detail


DNA-dependent activator of IFN-regulatory factors enhances the transcription of HIV-1 through NF-κB.
MedLine Citation:
PMID:  20599623     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pattern recognition receptors (PRRs) play a pivotal role in host innate immune responses against microbial infection. Viruses are primarily recognized by PRRs such as Toll-like receptor 3, 7, 8 and 9, and RIG-I-like receptors. Recent studies have demonstrated that DNA-dependent activator of IFN-regulatory factors (DAI) is a cytosolic sensor molecule for dsDNA, and is implicated in antiviral responses to some DNA viruses. Soon after infection, human immunodeficiency virus type-1 (HIV-1) synthesizes viral dsDNA in the cytoplasm by reverse transcriptase. In addition, an immune compromised state due to chronic HIV-1 infection results in opportunistic infection with some microbes that potentially activate DAI. However, it has not been elucidated whether DAI affects HIV-1 replication, or its possible mechanisms. Here, we showed that forced expression of DAI markedly enhanced HIV-1 replication, which was largely impaired by mutations at κB sites in HIV-1 LTR or by suppressing activation of NF-κB. Moreover, intact structure around the D3 region (174-232 aa) and two RIP homotypic interaction motifs (198-214 aa and 256-272 aa) within DAI were critical for its activity. These results suggest that activation of DAI might contribute to augment HIV-1 replication through DAI- NF-κB pathway.
Authors:
Takaya Hayashi; Hironori Nishitsuji; Ayako Takamori; Atsuhiko Hasegawa; Takao Masuda; Mari Kannagi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-22
Journal Detail:
Title:  Microbes and infection / Institut Pasteur     Volume:  12     ISSN:  1769-714X     ISO Abbreviation:  Microbes Infect.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-25     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883508     Medline TA:  Microbes Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  937-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.
Affiliation:
Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Viral*
HIV-1 / pathogenicity*,  physiology
Humans
NF-kappa B / metabolism*
Transcription, Genetic*
Virus Replication
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/NF-kappa B; 0/ZBP1 protein, human

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