Journal Article

Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus

Miyake, Kensuke, Khare, Reeti, Stewart, Phoebe L., Di Paolo, Nelson C., Acchione, Mauro, Doronin, Konstantin, Ohto, Umeharu, Beyer, Richard P., Shayakhmetov, Dmitry M., Kalyuzhniy, Oleksandr, Bammler, Theo M., Shimizu, Toshiyuki, Flatt, Justin W., Sumida, John P., Farin, Frederico M., Akashi-Takamura, Sachiko, MacDonald, James W.

2012

Overview

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 kB-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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adenoviridae infections / Adenoviridae Infections - immunology / Adenoviridae Infections - metabolism / Adenoviridae Infections - virology / Adenovirus / Adenoviruses / Adenoviruses, Human - genetics / Adenoviruses, Human - immunology / Adenoviruses, Human - metabolism / Animals / Binding / Biological and medical sciences / Blood / blood coagulation / Capsid / Capsid Proteins - chemistry / Capsid Proteins - genetics / Capsid Proteins - metabolism / Cascades / Cell Line, Tumor / Chemokines / CHO Cells / Coagulation / Cricetinae / Cricetulus / Crustaceans / Cryoelectron Microscopy / Cytokines / Cytokines - metabolism / Factor X - chemistry / Factor X - metabolism / Fundamental and applied biological sciences. Psychology / Gene Expression Profiling / Gene Expression Regulation / Genes / Hepatocytes - virology / Human / Humans / Immune response / Immunity / Immunity (Disease) / Immunity, Innate / Infections / Innate immunity / Living fossils / Macrophages / Macrophages - metabolism / Macrophages - virology / Mice / Mice, Inbred C57BL / Microbiology / Molecular Dynamics Simulation / mutants / Mutation / NF-kappa B - metabolism / Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains / Signal Transduction / Spleen / Structural analysis / Structural Analysis (Linguistics) / Structural Analysis (Science) / tissue repair / transcription (genetics) / Virology / Virus Internalization / Viruses / Wound healing