Coagulation factor X activates innate immunity to human species C adenovirus.
Coagulation factor X activates innate immunity to human species C adenovirus.
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DOI：
10.1126/science.1226625
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发表时间：
2012-11-09
期刊：
影响因子：
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通讯作者：
Shayakhmetov DM
中科院分区：
文献类型：
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作者：
Doronin K;Flatt JW;Di Paolo NC;Khare R;Kalyuzhniy O;Acchione M;Sumida JP;Ohto U;Shimizu T;Akashi-Takamura S;Miyake K;MacDonald JW;Bammler TK;Beyer RP;Farin FM;Stewart PL;Shayakhmetov DM
虽然凝血因子在鲎等“活化石”的宿主防御中发挥作用，但凝血系统在高等生物免疫中的作用仍不清楚。我们模拟了人类C型腺病毒（HAdv）与凝血因子X（FX）相互作用的界面，并引入了一个突变，消除了HAdv-FX复合物的形成。体内全基因组转录谱分析显示，FX结合消融的病毒未能激活由TLR 4/MyD 88/TRIF/TRAF 6信号下游的HAdv-FX复合物激活的核因子κ B依赖性早期应答基因的独特网络。我们的研究暗示宿主因子“装饰”的病毒作为一种机制，以触发先天免疫传感器，响应从血液到细胞内巨噬细胞区室的凝血FX的错位后，病毒进入细胞。
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.