Diab Mohammad, Vitenshtein Alon, Drori Yaron, Yamin Rachel, Danziger Oded, Zamostiano Rachel, Mandelboim Michal, Bacharach Eran, Mandelboim Ofer
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.
Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel.
Oncotarget. 2016 Oct 11;7(41):66468-66479. doi: 10.18632/oncotarget.11979.
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.
先天传感系统配备有专门识别各种病原体分子结构(病原体相关分子模式,PAMPs)的模式识别受体(PRRs)。这会导致抗病毒基因的诱导和病毒生长的抑制。人偏肺病毒(HMPV)是一种主要的呼吸道病毒,可引起儿童上、下呼吸道感染。在本研究中,我们表明,在HMPV感染后,先天传感系统通过RIG-I传感器检测病毒RNA,从而导致癌胚抗原相关细胞粘附分子1(CEACAM1)表达的诱导。我们进一步表明,CEACAM1是通过干扰素调节因子3(IRF3)与CEACAM1启动子的结合而被诱导的。我们证明,CEACAM1的诱导通过以SHP2依赖的方式抑制受感染细胞中的翻译机制来抑制病毒载量。总之,我们在此表明,HMPV感染的细胞上调CEACAM1以限制HMPV感染。