PDF(Pubmed)
Abstract：
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.
摘要：
甲型流感病毒(IAV)继续对全球畜牧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开发抗流感药物的潜在新靶标尤为重要。在这里，我们确定羟酰基辅酶A脱水酶3（HACD3）是支持IAV复制的新宿主因子。下调HACD3的表达降低了IAV感染的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PB1mRNA水平无影响,但可促进溶酶体介导的PB1蛋白自噬降解。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PB1参与SQSTM1/p62介导的自噬降解。总的来说，这些发现证实HACD3通过稳定病毒PB1蛋白在IAV复制中发挥正调节作用.
