Oncotarget

Research Papers: Immunology:

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

Mohammad Diab, Alon Vitenshtein, Yaron Drori, Rachel Yamin, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Eran Bacharach and Ofer Mandelboim _

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Oncotarget. 2016; 7:66468-66479. https://doi.org/10.18632/oncotarget.11979

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Abstract

Mohammad Diab1,*, Alon Vitenshtein1,*, Yaron Drori2,3, Rachel Yamin1, Oded Danziger4, Rachel Zamostiano4, Michal Mandelboim2,3, Eran Bacharach4 and Ofer Mandelboim1

1 The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel

2 Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel

3 Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

4 Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

* These authors have equally contributed to this work

Correspondence to:

Ofer Mandelboim, email:

Keywords: HMPV, CEACAM1, PRRs, PAMPs, RLRs, Immunology and Microbiology Section, Immune response, Immunity

Received: July 18, 2016 Accepted: September 01, 2016 Published: September 12, 2016

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.


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