Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 6, Issue 4, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mju015
Keywords
innate immunity; immune evasion; severe fever with thrombocytopenia syndrome virus; inclusion bodies; TBK1; IKK epsilon; spatial isolation
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Funding
- National Science Foundation of China [31125003, 31321001]
- Science and Technology Basic Work Program [2013FY113500]
- National Basic Research Program (973 Program) of China [2010CB530100, 2013CB911101]
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For antiviral signaling mediated by retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), the recruitment of cytosolic RLRs and downstream molecules (such as TBK1 and IKK epsilon) 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/IKK epsilon from mitochondrial 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/IKK epsilon-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 IBs are utilized to compartmentalize TBK1/IKK epsilon. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKK epsilon may participate in antiviral complex assembly, leading to the blockage of IFN induction. This study proposes a new role of viral IBs 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.
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