Japanese Encephalitis Virus NS1′ Protein Antagonizes Interferon Beta Production
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Japanese encephalitis virus (JEV) is a mosquito-borne virus and the major cause of viral encephalitis in Asia. NS1′, a 52-amino acid C-terminal extension of NS1, is generated with a -1 programmed ribosomal frameshift and is only present in members of the Japanese encephalitis serogroup of flaviviruses. Previous studies demonstrated that NS1′ plays a vital role in virulence, but the mechanism is unclear. In this study, an NS1′ defected (rG66A) virus was generated. We found that rG66A virus was less virulent than its parent virus (pSA14) in wild-type mice. However, similar mortality caused by the two viruses was observed in an IFNAR knockout mouse model. Moreover, we found that rG66A virus induced a greater type I interferon (IFN) response than that by pSA14, and JEV NS1′ significantly inhibited the production of IFN-β and IFN-stimulated genes. Taken together, our results reveal that NS1′ plays a vital role in blocking type I IFN production to help JEV evade antiviral immunity and benefit viral replication.
KeywordsJapanese encephalitis virus (JEV) NS1′ Type I interferon (IFN-I) Immune evasion
This work was supported by the National Key Research and Development Program of China (2016YFD0500407), National Natural Science Foundation of China (31502065 and 31572517), and Fundamental Research Funds for the Central Universities (2013PY051, 2662016Q003, and 2662015PY083).
JY, SBC, YFS, MC, and HCC conceived and designed the experiments. DYZ, FJ, QYL, LPZ, ZC, and ZKZ performed the experiments. DYZ analyzed the data. DYZ and JY wrote the manuscript and prepared the Figures. JY and SBC checked and finalized the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interests. All authors read and approved the final manuscript.
Animal and Human Rights Statement
Animal experiments in this study were approved by the Scientific Ethics Committee of Huazhong Agricultural University (permit number HZAUMO-2017-016).
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