title: Coagulation factor X activates innate immunity to human species C adenovirus.
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 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.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Doronin
authors.forename: Justin W
authors.initials: JW
authors.lastname: Flatt
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Di Paolo
authors.forename: Reeti
authors.initials: R
authors.lastname: Khare
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Kalyuzhniy
authors.forename: Mauro
authors.initials: M
authors.lastname: Acchione
authors.forename: John P
authors.initials: JP
authors.lastname: Sumida
authors.forename: Umeharu
authors.initials: U
authors.lastname: Ohto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Akashi-Takamura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.forename: James W
authors.initials: JW
authors.lastname: MacDonald
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.forename: Richard P
authors.initials: RP
authors.lastname: Beyer
authors.forename: Frederico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Shayakhmetov
mesh_terms: D000257:Adenoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D020285:Cryoelectron Microscopy; D016207:Cytokines / Q000378:metabolism; D005170:Factor X / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D056004:Molecular Dynamics Simulation; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; D016328:NF-kappa B; C018315:hexon capsid protein, Adenovirus; D005170:Factor X