Document Detail


DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells.
MedLine Citation:
PMID:  21703541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and the adaptor molecule TRIF, by isolation and sequencing of poly I:C-binding proteins in myeloid dendritic cells (mDCs). Knockdown of each helicase or TRIF by shRNA blocked the ability of mDCs to mount type I interferon (IFN) and cytokine responses to poly I:C, influenza A virus, and reovirus. Although DDX1 bound poly I:C via its Helicase A domain, DHX36 and DDX21 bound the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs.
Authors:
Zhiqiang Zhang; Taeil Kim; Musheng Bao; Valeria Facchinetti; Sung Yun Jung; Amir Ali Ghaffari; Jun Qin; Genhong Cheng; Yong-Jun Liu
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Immunity     Volume:  34     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-27     Completed Date:  2011-08-22     Revised Date:  2012-03-14    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  866-78     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Vesicular Transport / immunology*,  metabolism
Animals
Cell Line
DEAD-box RNA Helicases / genetics,  immunology*,  metabolism
Dendritic Cells / immunology*,  metabolism
Humans
Mice
Protein Binding
RNA, Double-Stranded / genetics*
Signal Transduction
Grant Support
ID/Acronym/Agency:
R01 AI056154-08/AI/NIAID NIH HHS; R01 AI069120-07/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Vesicular Transport; 0/RNA, Double-Stranded; 0/TICAM-1 protein, mouse; EC 2.7.7.-/DDX1 protein, mouse; EC 2.7.7.-/DDX21 protein, mouse; EC 3.6.1.-/DEAD-box RNA Helicases; EC 3.6.1.-/Dhx36 protein, mouse
Comments/Corrections
Comment In:
Nat Rev Immunol. 2011 Aug;11(8):504   [PMID:  21738218 ]

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