Zika virus NS5 protein antagonizes type I interferon production via blocking TBK1 activation.

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TitleZika virus NS5 protein antagonizes type I interferon production via blocking TBK1 activation.
Publication TypeJournal Article
Year of Publication2019
AuthorsLin, S, Yang, S, He, J, Guest, JD, Ma, Z, Yang, L, Pierce, BG, Tang, Q, Zhang, Y-J
JournalVirology
Volume527
Pagination180-187
Date Published2019 Jan 15
ISSN1096-0341
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.

DOI10.1016/j.virol.2018.11.009
Alternate JournalVirology
PubMed ID30530224