CEACAM1-Mediated Inhibition of Virus Production

Alon Vitenshtein, Yiska Weisblum, Sebastian Hauka, Anne Halenius, Esther Oiknine-Djian, Pinchas Tsukerman, Yoav Bauman, Yotam Bar-On, Noam Stern-Ginossar, Jonatan Enk, Rona Ortenberg, Julie Tai, Gal Markel, Richard S. Blumberg, Hartmut Hengel, Stipan Jonjic, Dana G. Wolf, Heiko Adler, Robert Kammerer, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageAmerican English
Pages (from-to)2331-2339
Number of pages9
JournalCell Reports
Issue number11
StatePublished - 14 Jun 2016

Bibliographical note

Funding Information:
This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 320473-BacNK. Additional support came from the Israel Science Foundation, the GIF foundation, the ICRF professorship grant, and the Helmholtz Israel grant (all to O.M.). This work was also supported by grants from the Israel Science Foundation (grant no. 275/13); the Israeli Ministry of Health (grant no. 10998); the European Union Seventh Framework Programme 562 FP7/2012-2016 (grant agreement no. 316655); and the Samueli Institute Brain Mind & Healing Center, under a contract from the US Army Medical Research and Materiel Command (USAMRAA award no. W81XWH-10-1-0938), within the TATRC portfolio of Integrative Medicine Research. We would like to kindly thank Beatrix Steer and Franziska Thomas for their assistance in studying the dynamics of MCMV and mCEACAM1 and Ihab Ansari for assistance with the ChIP experiments. O.M. is a Crown Professor of Molecular Immunology.

Publisher Copyright:
© 2016 The Authors.


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