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J Mol Cell Biol. 2014 Aug;6(4):324-37. doi: 10.1093/jmcb/mju015. Epub 2014 Apr 4.

Viral suppression of innate immunity via spatial isolation of TBK1/IKKε from mitochondrial antiviral platform.

Author information

1
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
2
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
3
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China h.wang@wh.iov.cn huzh@wh.iov.cn.

Abstract

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 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 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/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 IBs are utilized to compartmentalize TBK1/IKKε. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKKε 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.

KEYWORDS:

TBK1/IKKε; immune evasion; inclusion bodies; innate immunity; severe fever with thrombocytopenia syndrome virus; spatial isolation

PMID:
24706939
DOI:
10.1093/jmcb/mju015
[Indexed for MEDLINE]

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