CEACAM1-Mediated Inhibition of Virus Production

Cell Rep. 2016 Jun 14;15(11):2331-9. doi: 10.1016/j.celrep.2016.05.036. Epub 2016 Jun 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / virology
  • DEAD Box Protein 58 / metabolism
  • DNA, Viral / metabolism
  • Humans
  • Influenza, Human / metabolism
  • Influenza, Human / virology
  • Interferon Regulatory Factor-3 / metabolism
  • Mice
  • Organ Culture Techniques
  • Orthomyxoviridae / physiology*
  • Protein Biosynthesis
  • TOR Serine-Threonine Kinases / metabolism
  • Virus Replication

Substances

  • Antigens, CD
  • CD66 antigens
  • Cell Adhesion Molecules
  • DNA, Viral
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • TOR Serine-Threonine Kinases
  • DDX58 protein, human
  • DEAD Box Protein 58