Vitenshtein Alon, Weisblum Yiska, Hauka Sebastian, Halenius Anne, Oiknine-Djian Esther, Tsukerman Pinchas, Bauman Yoav, Bar-On Yotam, Stern-Ginossar Noam, Enk Jonatan, Ortenberg Rona, Tai Julie, Markel Gal, Blumberg Richard S, Hengel Hartmut, Jonjic Stipan, Wolf Dana G, Adler Heiko, Kammerer Robert, Mandelboim Ofer
The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Cell Rep. 2016 Jun 14;15(11):2331-9. doi: 10.1016/j.celrep.2016.05.036. Epub 2016 Jun 2.
Cells in our body can induce hundreds of antiviral genes following virus sensing, many of which remain largely uncharacterized. CEACAM1 has been previously shown to be induced by various innate systems; however, the reason for such tight integration to innate sensing systems was not apparent. Here, we show that CEACAM1 is induced following detection of HCMV and influenza viruses by their respective DNA and RNA innate sensors, IFI16 and RIG-I. This induction is mediated by IRF3, which bound to an ISRE element present in the human, but not mouse, CEACAM1 promoter. Furthermore, we demonstrate that, upon induction, CEACAM1 suppresses both HCMV and influenza viruses in an SHP2-dependent process and achieves this broad antiviral efficacy by suppressing mTOR-mediated protein biosynthesis. Finally, we show that CEACAM1 also inhibits viral spread in ex vivo human decidua organ culture.
我们体内的细胞在感知病毒后可诱导数百种抗病毒基因，其中许多基因在很大程度上仍未被表征。先前已表明CEACAM1可被各种先天系统诱导；然而，其与先天传感系统紧密整合的原因并不明显。在此，我们表明，在人巨细胞病毒（HCMV）和流感病毒分别被其各自的DNA和RNA先天传感器IFI16和RIG-I检测到时，CEACAM1会被诱导。这种诱导由IRF3介导，IRF3与人类而非小鼠CEACAM1启动子中存在的ISRE元件结合。此外，我们证明，诱导后，CEACAM1在一个依赖SHP2的过程中抑制HCMV和流感病毒，并通过抑制mTOR介导的蛋白质生物合成实现这种广泛的抗病毒功效。最后，我们表明CEACAM1也能抑制病毒在体外人蜕膜器官培养中的传播。
