CEACAM1-Mediated Inhibition of Virus Production

• DOI: 10.1016/j.celrep.2016.05.036
• Publication Date: 2016-06-03T03:51:47Z
• Authors: 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
• Keywords: QH301-705.5; 610; Cytomegalovirus; Virus Replication; Mice; 03 medical and health sciences; Organ Culture Techniques; Antigens, CD; Report; Influenza, Human; Animals; Humans; supression of mTOR acrivation; Biology (General); Receptors, Immunologic; CEACAM1; HCMV; CEACAM1; HCMV; innate sensors IFI16 and RIG-I; IFR3; supression of mTOR acrivation ;; 0303 health sciences; TOR Serine-Threonine Kinases; BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.; Orthomyxoviridae; 3. Good health; IFR3; Protein Biosynthesis; Cytomegalovirus Infections; DNA, Viral; DEAD Box Protein 58; Interferon Regulatory Factor-3; BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.; innate sensors IFI16 and RIG-I; Cell Adhesion Molecules

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.