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Science 338 (6108): 795-798

Copyright © 2012 by the American Association for the Advancement of Science

Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus

Konstantin Doronin,1,* Justin W. Flatt,2,* Nelson C. Di Paolo,1,* Reeti Khare,1 Oleksandr Kalyuzhniy,3,{dagger} Mauro Acchione,4 John P. Sumida,4 Umeharu Ohto,5,6 Toshiyuki Shimizu,5,6 Sachiko Akashi-Takamura,7 Kensuke Miyake,7,8 James W. MacDonald,9 Theo K. Bammler,9 Richard P. Beyer,9 Frederico M. Farin,9 Phoebe L. Stewart,2 Dmitry M. Shayakhmetov1,{ddagger}

Abstract: 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 {kappa}B–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.

1 Department of Medicine, University of Washington, Seattle, WA 98195, USA.
2 Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
3 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
4 Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
5 Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
6 RIKEN SPring-8 Center, Kouto 1-1-1, Sayo, Hyogo 679-5148, Japan.
7 Division of Innate Immunity, Department of Microbiology and Immunology, University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639, Japan.
8 Laboratory of Innate Immunity, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639, Japan.
9 Functional Genomics and Proteomics Core Facility, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.

* These authors contributed equally to this work.

{dagger} Present address: Neutralizing Antibody Center, International AIDS Vaccine Initiative, Scripps Research Institute, La Jolla, CA 92037, USA.

{ddagger} To whom correspondence should be addressed. E-mail: dshax{at}uw.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Decorated Virus Cannot Hide.
R. W. Herzog and D. A. Ostrov (2012)
Science 338, 748-749
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