State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Viruses. 2024 Apr 29;16(5):702. doi: 10.3390/v16050702.
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 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.
甲型流感病毒（IAV）继续对全球动物产业和公共卫生安全构成严重威胁。鉴定参与 IAV 生命周期的关键宿主因子，并阐明其作用的潜在机制，对于发现抗流感药物的潜在新靶标尤为重要。在此，我们鉴定出羟酰基辅酶 A 脱水酶 3（HACD3）是支持 IAV 复制的新宿主因子。下调 HACD3 的表达水平会降低 IAV 感染细胞和瞬时转染表达 PB1 的细胞中病毒 PB1 蛋白的水平。沉默 HACD3 表达对 mRNA 水平没有影响，但可以促进 PB1 蛋白溶酶体介导的自噬降解。进一步的研究表明，HACD3 与 PB1 和选择性自噬受体 SQSTM1/p62 相互作用，HACD3 与 SQSTM1/p62 竞争与 PB1 的相互作用，从而阻止 PB1 被 SQSTM1/p62 介导的自噬降解。总的来说，这些发现表明 HACD3 通过稳定病毒 PB1 蛋白在 IAV 复制中发挥正向调节作用。
