Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by...Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.展开更多
病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RI...病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RIG-I样受体(RIG-I like receptors,RLRs)、Nod样受体(Nod like receptors,NLRs)、Hin-200家族蛋白及一些DNA受体,这些受体介导一型干扰素及炎性细胞因子的产生,并受到多种严格的调控机制调控。该文将对模式识别受体介导的抗病毒天然免疫信号转导通路及相关调控分子机制做一综述。展开更多
Viral infection triggers activation of the transcription factors NF-KB and IRF3, which collaborate to induce the expression of type I interferons （IFNs） and elicit innate antiviral response. In this report, we ident...Viral infection triggers activation of the transcription factors NF-KB and IRF3, which collaborate to induce the expression of type I interferons （IFNs） and elicit innate antiviral response. In this report, we identified Kr（ippel-like factor 4 （KLF4）as a negative regulator of virus-triggered signaling. Overexpression of KLF4 inhibited virus-induced activation of ISRE and IFN-β promoter in various types of cells, while knockdown of KLF4 potentiated viral infection-triggered induction of IFNB1 and downstream genes and attenuated viral replication. In addition, KLF4 was found to be localized in the cytosol and nucleus, and viral infection promoted the translocation of KLF4 from cytosol to nucleus. Upon virus infection, KLF4 was bound to the promoter of IFNBgene and inhibited the recruitment of IRF3 to the IFNB promoter. Our study thus suggests that KLF4 negatively regulates cellular antiviral resonse.展开更多
The tripartite motif-containing （TRIM） proteins represent the largest E3 ubiquitin Ugase family. The multifaceted roles of TRIM38 in innate immunity and inflammation have been intensively investigated in recent year...The tripartite motif-containing （TRIM） proteins represent the largest E3 ubiquitin Ugase family. The multifaceted roles of TRIM38 in innate immunity and inflammation have been intensively investigated in recent years. TRIM38 is essential for cytosolic RNA or DNA sensor-mediated innate immune responses to both RNA and DNA viruses, while negatively regulating TLR3/4- and TNF/IL-1β-triggered inflammatory responses. In these processes, TRIM38 acts as an E3 ubiquitin or SUMO ligase, which targets key cellular signaling components, or as an enzymatic activity-independent regulator. This review summarizes recent advances that highlight the critical roles of TRIM38 in the reeulation of Droner innate immune and inflammatorv responses.展开更多
Interferon regulatory factor （IRF） 7 has been demonstrated to be a master regulator of virus-induced type I interferon production （IFN）, and it plays a central role in the innate immune response against viruses. H...Interferon regulatory factor （IRF） 7 has been demonstrated to be a master regulator of virus-induced type I interferon production （IFN）, and it plays a central role in the innate immune response against viruses. Here, we identified death-associated protein kinase 1 （DAPK1） as an IRF7-interacting protein by tandem affinity purification （TAP）. Viral infection induced DAPKI-IRF7 and DAPKI-IRF3 interactions and overexpression of DAPK1 enhanced virus-induced activation of the interferon-stimulated response element （ISRE） and IFN-p promoters and the expression of the IFNB1 gene. Knockdown of DAPK1 attenuated the induction of IFNB1 and RIG.lexpression triggered by viral infection or I FN-p, and they were enhanced by viral replication. In addition, viral infection or IFN-p treatment induced the expression of DAPK1. IFN-p treatment also activated DAPK1 by decreasing its phosphorylation level at serine 308. Interestingly, the involvement of DAPK1 in virus-induced signaling was independent of its kinase activity. Therefore, our study identified DAPK1 as an important regulator of the cellular antiviral response.展开更多
文摘Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.
文摘病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RIG-I样受体(RIG-I like receptors,RLRs)、Nod样受体(Nod like receptors,NLRs)、Hin-200家族蛋白及一些DNA受体,这些受体介导一型干扰素及炎性细胞因子的产生,并受到多种严格的调控机制调控。该文将对模式识别受体介导的抗病毒天然免疫信号转导通路及相关调控分子机制做一综述。
文摘Viral infection triggers activation of the transcription factors NF-KB and IRF3, which collaborate to induce the expression of type I interferons （IFNs） and elicit innate antiviral response. In this report, we identified Kr（ippel-like factor 4 （KLF4）as a negative regulator of virus-triggered signaling. Overexpression of KLF4 inhibited virus-induced activation of ISRE and IFN-β promoter in various types of cells, while knockdown of KLF4 potentiated viral infection-triggered induction of IFNB1 and downstream genes and attenuated viral replication. In addition, KLF4 was found to be localized in the cytosol and nucleus, and viral infection promoted the translocation of KLF4 from cytosol to nucleus. Upon virus infection, KLF4 was bound to the promoter of IFNBgene and inhibited the recruitment of IRF3 to the IFNB promoter. Our study thus suggests that KLF4 negatively regulates cellular antiviral resonse.
基金We thank members of the Shu laboratory for helpful discussions. The work in the authors＇ laboratory is supported by grants from the Ministry of Science and Technology of China （2016YFA0502102, 2014CB910103）, the National Natural Science Foundation of China （3163000013, 31521091, and 91429304） and National Postdoctoral Program for Innovative Talents （BX201600116）.
文摘The tripartite motif-containing （TRIM） proteins represent the largest E3 ubiquitin Ugase family. The multifaceted roles of TRIM38 in innate immunity and inflammation have been intensively investigated in recent years. TRIM38 is essential for cytosolic RNA or DNA sensor-mediated innate immune responses to both RNA and DNA viruses, while negatively regulating TLR3/4- and TNF/IL-1β-triggered inflammatory responses. In these processes, TRIM38 acts as an E3 ubiquitin or SUMO ligase, which targets key cellular signaling components, or as an enzymatic activity-independent regulator. This review summarizes recent advances that highlight the critical roles of TRIM38 in the reeulation of Droner innate immune and inflammatorv responses.
文摘Interferon regulatory factor （IRF） 7 has been demonstrated to be a master regulator of virus-induced type I interferon production （IFN）, and it plays a central role in the innate immune response against viruses. Here, we identified death-associated protein kinase 1 （DAPK1） as an IRF7-interacting protein by tandem affinity purification （TAP）. Viral infection induced DAPKI-IRF7 and DAPKI-IRF3 interactions and overexpression of DAPK1 enhanced virus-induced activation of the interferon-stimulated response element （ISRE） and IFN-p promoters and the expression of the IFNB1 gene. Knockdown of DAPK1 attenuated the induction of IFNB1 and RIG.lexpression triggered by viral infection or I FN-p, and they were enhanced by viral replication. In addition, viral infection or IFN-p treatment induced the expression of DAPK1. IFN-p treatment also activated DAPK1 by decreasing its phosphorylation level at serine 308. Interestingly, the involvement of DAPK1 in virus-induced signaling was independent of its kinase activity. Therefore, our study identified DAPK1 as an important regulator of the cellular antiviral response.
