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

doi:10.1016/j.celrep.2016.05.036

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

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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 language	American English
Pages (from-to)	2331-2339
Number of pages	9
Journal	Cell Reports
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2016.05.036
State	Published - 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.

Access to Document

10.1016/j.celrep.2016.05.036

Cite this

Vitenshtein, A., Weisblum, Y., Hauka, S., Halenius, A., Oiknine-Djian, E., Tsukerman, P., Bauman, Y., Bar-On, Y., Stern-Ginossar, N., Enk, J., Ortenberg, R., Tai, J., Markel, G., Blumberg, R. S., Hengel, H., Jonjic, S., Wolf, D. G., Adler, H., Kammerer, R., & Mandelboim, O. (2016). CEACAM1-Mediated Inhibition of Virus Production. Cell Reports, 15(11), 2331-2339. https://doi.org/10.1016/j.celrep.2016.05.036

@article{dc9657518d3d40eab73f6b0dd0c7b8cb,

title = "CEACAM1-Mediated Inhibition of Virus Production",

abstract = "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.",

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

note = "Funding Information: This study was supported by the European Research Council under the European Union{\textquoteright}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: {\textcopyright} 2016 The Authors.",

year = "2016",

month = jun,

day = "14",

doi = "10.1016/j.celrep.2016.05.036",

language = "American English",

volume = "15",

pages = "2331--2339",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "11",

}

Vitenshtein, A, Weisblum, Y, Hauka, S, Halenius, A, Oiknine-Djian, E, Tsukerman, P, Bauman, Y, Bar-On, Y, Stern-Ginossar, N, Enk, J, Ortenberg, R, Tai, J, Markel, G, Blumberg, RS, Hengel, H, Jonjic, S, Wolf, DG, Adler, H, Kammerer, R & Mandelboim, O 2016, 'CEACAM1-Mediated Inhibition of Virus Production', Cell Reports, vol. 15, no. 11, pp. 2331-2339. https://doi.org/10.1016/j.celrep.2016.05.036

TY - JOUR

T1 - CEACAM1-Mediated Inhibition of Virus Production

AU - Vitenshtein, Alon

AU - Weisblum, Yiska

AU - Hauka, Sebastian

AU - Halenius, Anne

AU - Oiknine-Djian, Esther

AU - Tsukerman, Pinchas

AU - Bauman, Yoav

AU - Bar-On, Yotam

AU - Stern-Ginossar, Noam

AU - Enk, Jonatan

AU - Ortenberg, Rona

AU - Tai, Julie

AU - Markel, Gal

AU - Blumberg, Richard S.

AU - Hengel, Hartmut

AU - Jonjic, Stipan

AU - Wolf, Dana G.

AU - Adler, Heiko

AU - Kammerer, Robert

AU - Mandelboim, Ofer

N1 - 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.

PY - 2016/6/14

Y1 - 2016/6/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84974698225&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.05.036

DO - 10.1016/j.celrep.2016.05.036

M3 - Article

C2 - 27264178

AN - SCOPUS:84974698225

SN - 2211-1247

VL - 15

SP - 2331

EP - 2339

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

CEACAM1-Mediated Inhibition of Virus Production

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this