Coagulation factor X activates innate immunity to human species C adenovirus

Science. 2012 Nov 9;338(6108):795-8. doi: 10.1126/science.1226625. Epub 2012 Sep 27.


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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections / immunology*
  • Adenoviridae Infections / metabolism
  • Adenoviridae Infections / virology
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Adenoviruses, Human / metabolism*
  • Animals
  • CHO Cells
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Cryoelectron Microscopy
  • Cytokines / metabolism
  • Factor X / chemistry
  • Factor X / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hepatocytes / virology
  • Humans
  • Immunity, Innate*
  • Macrophages / metabolism
  • Macrophages / virology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Dynamics Simulation
  • Mutation
  • NF-kappa B / metabolism
  • Signal Transduction
  • Virus Internalization


  • Capsid Proteins
  • Cytokines
  • NF-kappa B
  • hexon capsid protein, Adenovirus
  • Factor X

Associated data

  • GEO/GSE36078