Journal
ONCOTARGET
Volume 7, Issue 41, Pages 66468-66479Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11979
Keywords
HMPV; CEACAM1; PRRs; PAMPs; RLRs; RIG-I; SHP2; Immunology and Microbiology Section; Immune response; Immunity
Categories
Funding
- European Research Council [320473-BacNK]
- Israel Science Foundation
- GIF foundation
- Lewis family foundation
- ICRF professorship grant
- Helmholtz Israel grant
- Rosetrees Trust
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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.
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