内部收益率3
干扰素调节因子
细胞生物学
免疫系统
干扰素
先天免疫系统
生物
TLR3型
信号转导
细胞凋亡
坦克结合激酶1
磷酸化
病毒学
免疫学
Toll样受体
蛋白激酶B
遗传学
MAP激酶激酶激酶
作者
Yujie Ren,An Wang,Bowen Zhang,Weidong Ji,Xiao-Xu Zhu,Jing Lou,Mingbin Huang,Yang Qiu,Xi Zhou
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-10-04
卷期号:9 (40)
标识
DOI:10.1126/sciadv.adi6586
摘要
Apoptotic inhibition and immune evasion have particular importance to efficient viral infection, while a dilemma often faced by viruses is that inhibiting apoptosis can up-regulate antiviral immune signaling. Herein, we uncovered that in addition to inhibiting caspase-8/extrinsic apoptosis, human cytomegalovirus (HCMV)-encoded UL36 suppresses interferon regulatory factor 3 (IRF3)-dependent immune signaling by directly targeting IRF3 to abrogate IRF3 interaction with stimulator of interferon genes or TANK-binding kinase 1 and inhibit IRF3 phosphorylation/activation. Although UL36-mediated caspase-8/extrinsic apoptosis inhibition enhances immune signaling, the immunosuppressing activity of UL36 counterbalances this immunoenhancing "side effect" undesirable for virus. Furthermore, we used mutational analyses to show that only the wild-type, but not the UL36 mutant losing either inhibitory activity, is sufficient to support effective HCMV replication in cells, showing the functional importance of the dual inhibition by UL36 for the HCMV life cycle. Together, our findings demonstrate a sophisticated mechanism by which HCMV tightly controls innate immune signaling and extrinsic apoptosis for efficient infection.
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