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Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus.
MedLine Citation:
PMID:  23019612     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Although coagulation factors play a role in host defense for "living fossils" such as horseshoe crabs, the role of the coagulation system in immunity in higher organisms remains unclear. Here, we modeled the interface of human species C adenovirus (HAdv) interaction with coagulation factor X (FX) and introduced a mutation that abrogated formation of HAdv-FX complex. In vivo genome-wide transcriptional profiling revealed that FX-binding-ablated virus failed to activate a distinct network of NF-κB-dependent early response genes that are activated by HAdv-FX complex downstream of TLR4/MyD88/TRIF/TRAF6 signaling. Our study implicates host factor "decoration" of the virus as a mechanism to trigger an innate immune sensor that responds to a misplacement of coagulation FX from the blood into intracellular macrophage compartments upon virus entry into the cell.
Authors:
Konstantin Doronin; Justin W Flatt; Nelson C Di Paolo; Reeti Khare; Oleksandr Kalyuzhniy; Mauro Acchione; John P Sumida; Umeharu Ohto; Toshiyuki Shimizu; Sachiko Akashi-Takamura; Kensuke Miyake; James W Macdonald; Theo K Bammler; Richard P Beyer; Frederico M Farin; Phoebe L Stewart; Dmitry M Shayakhmetov
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-27
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  -     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
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