Author: Qian, Wei; Wei, Xiaoqin; Guo, Kelei; Li, Yongtao; Lin, Xian; Zou, Zhong; Zhou, Hongbo; Jin, Meilin
Title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-ß Production by Targeting TNF Receptor-Associated Factor 3 Document date: 2017_7_3
ID: 00mqmpzw_4
Snippet: In view of several yet undetermined roles of NS1 in the inhibition of interferon, we conducted a study aimed to determine the importance of the function of the N-and/or C-terminal domains of the NS1 protein in immune evasion. By using the luciferase reporter assay, we were able to demonstrate that the C-terminal ED (AA126 to 225, named NS1/126-225) of the NS1 protein was sufficient to inhibit the production of IFN-β driven by RIG-I(N). Mechanist.....
Document: In view of several yet undetermined roles of NS1 in the inhibition of interferon, we conducted a study aimed to determine the importance of the function of the N-and/or C-terminal domains of the NS1 protein in immune evasion. By using the luciferase reporter assay, we were able to demonstrate that the C-terminal ED (AA126 to 225, named NS1/126-225) of the NS1 protein was sufficient to inhibit the production of IFN-β driven by RIG-I(N). Mechanistically, NS1/126-225 was found specifically to interact with TRAF3, to dissociate MAVS-TRAF3 complex, and to decrease K63-linked polyubiquitination of TRAF3. This was shown to result in reduced IRF3-dependent production of IFN-β, with subsequent enhancement of virus replication. These data reveal a novel mechanism for how the influenza A virus NS1 protein induces inhibition of the host IFN production and may provide a potential target for antiviral drug development.
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