Open AccessNuclear localization of Zika virus NS5 contributes to suppression of type I interferon production and response
Author(s) -
Zikai Zhao,
Mengying Tao,
Wei Han,
Zijing Fan,
Muhammad Imran,
Shengbo Cao,
Jing Ye
Publication year - 2021
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/jgv.0.001376
Subject(s) - biology , flavivirus , stat2 , zika virus , virology , irf3 , nuclear localization sequence , viral replication , interferon , innate immune system , transcription factor , nls , interferon type i , virus , microbiology and biotechnology , signal transduction , immunology , stat protein , immune system , genetics , gene , stat3 , nucleus
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus, which caused an unprecedented epidemic in Latin America. Among all viral non-structural proteins in flavivirus, NS5 is the most highly conserved and has multiple crucial functions, including participating in viral RNA replication and suppressing host innate immunity. Although ZIKV NS5 prominently localizes in the nucleus during infection, its specific nuclear localization signal (NLS), and its role in viral replication and pathogenesis remain controversial. Here, we identified aa 11-90 and aa 370-406 regions that contain NLSs, which are critical for nuclear localization of ZIKV NS5. Further experiments demonstrated that nuclear localization of ZIKV NS5 predominantly participates in suppression of interferon regulatory factor 3 (IRF3)-mediated activation of type I IFN (IFN-I) transcription and inhibition of IFN-I downstream response independent of its effect on signal transducers and activators of transcription 2 (STAT2) degradation. These results suggest that subcellular localization of NS5 is important for its function on innate immune suppression, which provides new insight into ZIKV pathogenesis.