National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China.
J Med Virol. 2023 Oct;95(10):e29171. doi: 10.1002/jmv.29171.
Influenza A virus (IAV) relies on intricate and highly coordinated associations with host factors for efficient replication and transmission. Characterization of such factors holds great significance for development of anti-IAV drugs. Our study identified protein arginine methyltransferase 5 (PRMT5) as a novel host factor indispensable for IAV replication. Silencing PRMT5 resulted in drastic repression of IAV replication. Our findings revealed that PRMT5 interacts with each protein component of viral ribonucleoproteins (vRNPs) and promotes arginine symmetric dimethylation of polymerase basic 2 (PB2). Overexpression of PRMT5 enhanced viral polymerase activity in a dose-dependent manner, emphasizing its role in genome transcription and replication of IAV. Moreover, analysis of PB2 protein sequences across various subtypes of IAVs demonstrated the high conservation of potential RG motifs recognized by PRMT5. Overall, our study suggests that PRMT5 supports IAV replication by facilitating viral polymerase activity by interacting with PB2 and promoting its arginine symmetric dimethylation. This study deepens our understanding of how IAV manipulates host factors to facilitate its replication and highlights the great potential of PRMT5 to serve as an anti-IAV therapeutic target.
甲型流感病毒（IAV）依靠与宿主因子的复杂而高度协调的关联来实现有效的复制和传播。对这些因子的特性进行描述对于开发抗 IAV 药物具有重要意义。我们的研究确定了蛋白质精氨酸甲基转移酶 5（PRMT5）是 IAV 复制所必需的新型宿主因子。沉默 PRMT5 会严重抑制 IAV 的复制。我们的研究结果表明，PRMT5 与病毒核糖核蛋白（vRNP）的每个蛋白成分相互作用，并促进聚合酶碱性 2（PB2）的精氨酸对称二甲基化。PRMT5 的过表达以剂量依赖性方式增强了病毒聚合酶的活性，强调了其在 IAV 基因组转录和复制中的作用。此外，对不同亚型的 IAV 的 PB2 蛋白序列的分析表明，PRMT5 识别的潜在 RG 基序高度保守。总的来说，我们的研究表明，PRMT5 通过与 PB2 相互作用并促进其精氨酸对称二甲基化来支持 IAV 复制，从而增强病毒聚合酶的活性。这项研究加深了我们对 IAV 如何操纵宿主因子以促进其复制的理解，并强调了 PRMT5 作为抗 IAV 治疗靶标的巨大潜力。
