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NS5 Conservative Site Is Required for Zika Virus to Restrict the RIG-I Signaling.


ABSTRACT: During host-virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defending pathogen infections. NS5 subsequently represses K63-linked polyubiquitination of RIG-I, attenuates the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3), and inhibits the expression and production of interferon-? (IFN-?), thereby restricting the RIG-I signaling pathway. Interestingly, we demonstrate that the methyltransferase (MTase) domain of NS5 is required for the repression of RIG-I ubiquitination, IRF3 activation, and IFN-? production. Detailed studies further reveal that the conservative active site D146 of NS5 is critical for the suppression of the RIG-I signaling. Therefore, we uncover an essential role of NS5 conservative site D146 in ZIKV-mediated repression of innate immune system, illustrate a distinct mechanism by which ZIKV evades host immune responses, and discover a potential target for anti-viral infection.

SUBMITTER: Li A 

PROVIDER: S-EPMC7033454 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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NS5 Conservative Site Is Required for Zika Virus to Restrict the RIG-I Signaling.

Li Aixin A   Wang Wenbiao W   Wang Yingchong Y   Chen Keli K   Xiao Feng F   Hu Dingwen D   Hui Lixia L   Liu Weiyong W   Feng Yuqian Y   Li Geng G   Tan Qiuping Q   Liu Yingle Y   Wu Kailang K   Wu Jianguo J  

Frontiers in immunology 20200214


During host-virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defe  ...[more]

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