1. Zika virus NS5 protein antagonizes type I interferon production via blocking TBK1 activation.
- Author
-
Lin, Shaoli, Yang, Shixing, He, Jia, Guest, Johnathan D., Ma, Zexu, Yang, Liping, Pierce, Brian G., Tang, Qiyi, and Zhang, Yan-Jin
- Subjects
- *
ZIKA virus , *INTERFERONS , *UBIQUITIN , *PHOSPHORYLATION , *TUMOR necrosis factors - Abstract
Abstract Zika virus (ZIKV) is a mosquito-borne positive-sense single-stranded RNA virus in the family of Flaviviridae. Unlike other flaviviruses, ZIKV infection of pregnant women may result in birth defects in their newborns, such as microcephaly or vision problem. ZIKV is known to antagonize the interferon (IFN) production in infected cells. However, the exact mechanism of this interference is not fully understood. Here, we demonstrate that NS5 protein of ZIKV MR766 strain antagonizes IFN production through inhibiting the activation of TANK-binding kinase 1 (TBK1), which phosphorylates the transcription activator IFN regulatory factor 3 (IRF3). Mechanistically, NS5 interacts with the ubiquitin-like domain of TBK1 and results in less complex of TBK1 and TNF (tumor necrosis factor) receptor-associated factor 6 (TRAF6), leading to dampened TBK1 activation and IRF3 phosphorylation. Our study provides insights into the mechanism of ZIKV evasion of IFN-mediated innate immunity. Highlights • ZIKV NS5 antagonizes IFN production through inhibiting the activation of TBK1. • NS5 interacts with the ubiquitin-like domain of TBK1. • Both MT and RdRp domains of NS5 are needed for NS5 to interact with TBK1. • NS5 interaction with TBK1 leads to less TBK1 in complex with TRAF6. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF