HACD3 Prevents PB1 from Autophagic Degradation to Facilitate the Replication of Influenza A Virus

文献类型： 外文期刊

第一作者： Li, Qibing

作者： Li, Qibing;Jiang, Li;Wang, Yihan;Liu, Xuwei;Wang, Bo;Shan, Zhibo;Wang, Yi-Han;Wang, Yuqin;Chen, Hualan;Li, Chengjun

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关键词： HACD3; influenza A virus; replication; PB1; autophagy

期刊名称：VIRUSES-BASEL （ 影响因子：4.7； 五年影响因子：4.8 ）

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年卷期： 2024 年 16 卷 5 期

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收录情况： SCI

摘要： Influenza A virus (IAV) continues to pose serious threats to the global animal industry and public health security. Identification of critical host factors engaged in the life cycle of IAV and elucidation of the underlying mechanisms of their action are particularly important for the discovery of potential new targets for the development of anti-influenza drugs. Herein, we identified Hydroxyacyl-CoA Dehydratase 3 (HACD3) as a new host factor that supports the replication of IAV. Downregulating the expression of HACD3 reduced the level of viral PB1 protein in IAV-infected cells and in cells that were transiently transfected to express PB1. Silencing HACD3 expression had no effect on the level of PB1 mRNA but could promote the lysosome-mediated autophagic degradation of PB1 protein. Further investigation revealed that HACD3 interacted with PB1 and selective autophagic receptor SQSTM1/p62, and HACD3 competed with SQSTM1/p62 for the interaction with PB1, which prevented PB1 from SQSTM1/p62-mediated autophagic degradation. Collectively, these findings establish that HACD3 plays a positive regulatory role in IAV replication by stabilizing the viral PB1 protein.

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