The coagulation system protects our bodies from excessive loss of blood from a leaky or damaged vessel, whereas the immune system protects us from invading pathogens such as viruses. Unexpected links between these two systems suggest their coevolution.
Doronin et al. show that an essential protein for the clotting process binds to a virus that has entered the blood stream, thereby allowing the immune system to sense the invader and mount a rapid and potent antiviral response. They 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.