Suppression of human metapneumovirus (HMPV) infection by the innate sensing gene CEACAM1

Oncotarget. 2016 Oct 11;7(41):66468-66479. doi: 10.18632/oncotarget.11979.

Abstract

The innate sensing system is equipped with PRRs specialized in recognizing molecular structures (PAMPs) of various pathogens. This leads to the induction of anti-viral genes and inhibition of virus growth. Human Metapneumovirus (HMPV) is a major respiratory virus that causes an upper and lower respiratory tract infection in children. In this study we show that upon HMPV infection, the innate sensing system detects the viral RNA through the RIG-I sensor leading to induction of CEACAM1 expression. We further show that CEACAM1 is induced via binding of IRF3 to the CEACAM1 promoter. We demonstrate that induction of CEACAM1 suppresses the viral loads via inhibition of the translation machinery in the infected cells in an SHP2-dependent manner. In summary, we show here that HMPV-infected cells upregulates CEACAM1 to restrict HMPV infection.

Keywords: CEACAM1; HMPV; Immune response; Immunity; Immunology and Microbiology Section; PAMPs; PRRs; RIG-I; RLRs; SHP2.

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / immunology*
  • Chlorocebus aethiops
  • Humans
  • Immunity, Innate / immunology*
  • Metapneumovirus / immunology
  • Paramyxoviridae Infections / immunology*
  • Paramyxoviridae Infections / metabolism
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / metabolism
  • Respiratory Tract Infections / virology
  • Up-Regulation
  • Vero Cells

Substances

  • Antigens, CD
  • CD66 antigens
  • Cell Adhesion Molecules