For antiviral signaling mediated by retinoic acid-inducible gene I （RiG-I）-like receptors （RLRs）, the recruitment of cytosoUc RLRs and downstream molecules （such as TBK1 and IKKε） to mitochondriaL platform is a...For antiviral signaling mediated by retinoic acid-inducible gene I （RiG-I）-like receptors （RLRs）, the recruitment of cytosoUc RLRs and downstream molecules （such as TBK1 and IKKε） to mitochondriaL platform is a central event that facilitates the establishment of host antiviral state. Here, we present an example of viral targeting for immune evasion through spatial isolation of TBK1/IKKε from mitochond riai antiviral platform, which was employed by severe fever with thrombocytopenia syndrome virus （SFTSV）, a deadly bunyavirus emerging recently. We showed that SFTSV nonstructural protein NSs functions as the interferon （IFN） antagonist, mainly via suppressing TBK1/IKKε-IRF3 signaling. NSs mediates the formation of cytoplasmic inclusion bodies （IBs）, and the blockage of IB formation impairs IFN-inhibiting activity of NSs. We next demonstrate that I Bs are utilized to compartmentalize TBK1/I KKε. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKKε may participate in antiviral complex assembly, leadingto the blockage of lFN ind uction. This study proposes a new role of viral I Bs as virus-built＇jail＇ for imprisoning cellular factors and presents a novel and likely common mechanism of viral immune evasion through spatial isolation of critical signaling molecules from the mitochondrial antiviral platform.展开更多
基金Acknowtedgements We thank Dr Hong-Bing Shu （Wuhan University, China） for supplying reporter and expression plasmids. This work was supported by the National Science Foundation of China （grant numbers 31125003 and 31321001）, the Science and Technology Basic Work Program （grant number 2013FY113500）, and the National Basic Research Program （973 Program） of China （grant numbers 2010CB530100 and 2013CB911101）.
文摘For antiviral signaling mediated by retinoic acid-inducible gene I （RiG-I）-like receptors （RLRs）, the recruitment of cytosoUc RLRs and downstream molecules （such as TBK1 and IKKε） to mitochondriaL platform is a central event that facilitates the establishment of host antiviral state. Here, we present an example of viral targeting for immune evasion through spatial isolation of TBK1/IKKε from mitochond riai antiviral platform, which was employed by severe fever with thrombocytopenia syndrome virus （SFTSV）, a deadly bunyavirus emerging recently. We showed that SFTSV nonstructural protein NSs functions as the interferon （IFN） antagonist, mainly via suppressing TBK1/IKKε-IRF3 signaling. NSs mediates the formation of cytoplasmic inclusion bodies （IBs）, and the blockage of IB formation impairs IFN-inhibiting activity of NSs. We next demonstrate that I Bs are utilized to compartmentalize TBK1/I KKε. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKKε may participate in antiviral complex assembly, leadingto the blockage of lFN ind uction. This study proposes a new role of viral I Bs as virus-built＇jail＇ for imprisoning cellular factors and presents a novel and likely common mechanism of viral immune evasion through spatial isolation of critical signaling molecules from the mitochondrial antiviral platform.
