https://scholars.lib.ntu.edu.tw/handle/123456789/586011
標題: | Role of the Chaperone Protein 14-3-3ε in the Regulation of Influenza A Virus-Activated Beta Interferon | 作者: | Tam, Ee-Hong Liu, Yen-Chin Woung, Chian-Huey HELENE MINYI LIU Wu, Guan-Hong Wu, Chih-Ching Kuo, Rei-Lin |
關鍵字: | 14-3-3ε protein; NS1 protein; influenza A virus; interferon β | 公開日期: | 2021 | 卷: | 95 | 期: | 20 | 來源出版物: | Journal of virology | 摘要: | The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in retinoic acid-inducible gene I (RIG-I) translocation to mitochondrial antiviral-signaling protein (MAVS) to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C terminus-truncated NS1 with a T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in retinoic acid-inducible gene I (RIG-I) translocation that induces type I interferon (IFN) expression, and that NS1 protein prevents RIG-I translocation to the mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586011 | ISSN: | 0022538X | DOI: | 10.1128/JVI.00231-21 | SDG/關鍵字: | beta interferon; DDX58 protein, human; immunoglobulin receptor; INS1 protein, influenza virus; interferon; interferon regulatory factor 3; protein 14 3 3; retinoic acid inducible protein I; viral protein; virus RNA; genetics; host pathogen interaction; hu |
顯示於: | 生物化學暨分子生物學科研究所 |
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