CEACAM1-Mediated Inhibition of Virus Production

• IFI16 and RIG-I sensing of HCMV and influenza viruses induces expression of CEACAM1
• IRF3 directly binds the CEACAM1 promoter and mediates the induction of CEACAM1
• CEACAM1 suppresses mTOR activation and virus production in an SHP2-dependent manner
• CEACAM1 suppresses HCMV spread in human ex vivo organ culture model of infection

SummaryCells 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.

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