CEACAM1-Mediated Inhibition of Virus Production.
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.
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.
Alon
A
Vitenshtein
Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Yiska
Y
Weisblum
Institute for Virology, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Sebastian
S
Hauka
Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
Anne
A
Halenius
Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Esther
E
Oiknine-Djian
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.
Pinchas
P
Tsukerman
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.
Yoav
Y
Bauman
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.
Yotam
Y
Bar-On
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.
Noam
N
Stern-Ginossar
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.
Jonatan
J
Enk
Ella Institute of Melanoma, Cancer Research Center Sheba Medical Center, 5262000 Tel Hashomer, Israel; Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Rona
R
Ortenberg
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.
Julie
J
Tai
Ella Institute of Melanoma, Cancer Research Center Sheba Medical Center, 5262000 Tel Hashomer, Israel; Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Gal
G
Markel
Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Richard S
RS
Blumberg
Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
Hartmut
H
Hengel
Department of Histology and Embryology and Center for Proteomics, Faculty of Medicine, University of Rijeka, HR-51000 Rijeka, Croatia.
Stipan
S
Jonjic
Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Dana G
DG
Wolf
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Research Unit Gene Vectors, 81377 Munich, Germany.
Heiko
H
Adler
Institute of Immunology, Friedrich Loeffler Institute, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.
Robert
R
Kammerer
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. Electronic address: oferm@ekmd.huji.ac.il.
Ofer
O
Mandelboim
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000821:virology; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D006801:Humans; D007251:Influenza, Human / Q000378:metabolism / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D009975:Orthomyxoviridae / Q000502:physiology*; D014176:Protein Biosynthesis; D011971:Receptors, Immunologic; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014779:Virus Replication
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D004279:DNA, Viral; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D011971:Receptors, Immunologic; D058570:TOR Serine-Threonine Kinases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58