Document Detail

Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation.
MedLine Citation:
PMID:  16182584     Owner:  NLM     Status:  MEDLINE    
In this study, we found that infection with flaviviruses, such as Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2), leads to interferon-beta (IFN-beta) gene expression in a virus-replication- and de novo protein-synthesis-dependent manner. NF-kappaB activation is essential for IFN-beta induction in JEV- and DEN-2-infected cells. However, these two viruses seem to preferentially target different members of the interferon regulatory factor (IRF) family. The activation of constitutively expressed IRF-3, characterized by slower gel mobility, dimer formation, and nuclear translocation, is more evident in JEV-infected cells. Other members of the IRF family, such as IRF-1 and IRF-7 are also induced by DEN-2, but not by JEV infection. The upstream molecules responsible for IRF-3 and NF-kappaB activation were further studied. Evidently, a cellular RNA helicase, retinoic acid-inducible gene I (RIG-I), and a cellular kinase, phosphatidylinositol-3 kinase (PI3K), are required for flavivirus-induced IRF-3 and NF-kappaB activation, respectively. Therefore, we suggest that JEV and DEN-2 initiate the host innate immune response through a molecular mechanism involving RIG-I/IRF-3 and PI3K/NF-kappaB signaling pathways.
Tsung-Hsien Chang; Ching-Len Liao; Yi-Ling Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-15
Journal Detail:
Title:  Microbes and infection / Institut Pasteur     Volume:  8     ISSN:  1286-4579     ISO Abbreviation:  Microbes Infect.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-30     Completed Date:  2006-03-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100883508     Medline TA:  Microbes Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  157-71     Citation Subset:  IM    
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Cell Line
Cercopithecus aethiops
DEAD-box RNA Helicases
Dengue Virus / physiology
Encephalitis Virus, Japanese / physiology
Flavivirus / physiology*
Gene Expression Regulation*
Interferon Regulatory Factor-3 / metabolism*
Interferon-beta / genetics*
NF-kappa B / metabolism*
RNA Helicases / metabolism*
Vero Cells
Reg. No./Substance:
0/Interferon Regulatory Factor-3; 0/NF-kappa B; 77238-31-4/Interferon-beta; EC 3-Kinase; EC 2.7.7.-/RNA Helicases; EC 3.6.1.-/DDX58 protein, human; EC 3.6.1.-/DEAD-box RNA Helicases

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