Publication Date:
2012-09-29
Description:
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. We modeled the interface of human species C adenovirus (HAdv) interaction with coagulation factor X (FX) and introduced a mutation that abrogated formation of the HAdv-FX complex. In vivo genome-wide transcriptional profiling revealed that FX-binding-ablated virus failed to activate a distinct network of nuclear factor kappaB-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762479/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762479/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doronin, Konstantin -- Flatt, Justin W -- Di Paolo, Nelson C -- Khare, Reeti -- Kalyuzhniy, Oleksandr -- Acchione, Mauro -- Sumida, John P -- Ohto, Umeharu -- Shimizu, Toshiyuki -- Akashi-Takamura, Sachiko -- Miyake, Kensuke -- MacDonald, James W -- Bammler, Theo K -- Beyer, Richard P -- Farin, Frederico M -- Stewart, Phoebe L -- Shayakhmetov, Dmitry M -- AI065429/AI/NIAID NIH HHS/ -- CA141439/CA/NCI NIH HHS/ -- P30ES07033/ES/NIEHS NIH HHS/ -- R01 AI065429/AI/NIAID NIH HHS/ -- R01 CA141439/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):795-8. doi: 10.1126/science.1226625. Epub 2012 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23019612" target="_blank"〉PubMed〈/a〉
Keywords:
Adenoviridae Infections/*immunology/metabolism/virology
;
Adenoviruses, Human/genetics/*immunology/*metabolism
;
Animals
;
CHO Cells
;
Capsid Proteins/chemistry/genetics/metabolism
;
Cell Line, Tumor
;
Cricetinae
;
Cricetulus
;
Cryoelectron Microscopy
;
Cytokines/metabolism
;
Factor X/chemistry/*metabolism
;
Gene Expression Profiling
;
Gene Expression Regulation
;
Hepatocytes/virology
;
Humans
;
*Immunity, Innate
;
Macrophages/metabolism/virology
;
Mice
;
Mice, Inbred C57BL
;
Molecular Dynamics Simulation
;
Mutation
;
NF-kappa B/metabolism
;
Signal Transduction
;
Virus Internalization
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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