PRMT5 Facilitates Infectious Bursal Disease Virus Replication through Arginine Methylation of VP1
PRMT5 Facilitates Infectious Bursal Disease Virus Replication through Arginine Methylation of VP1
复制标题
DOI：
10.1128/jvi.01637-22
复制
发表时间：
2023-02-14
影响因子：
5.4
通讯作者：
Wu，Huansheng
中科院分区：
文献类型：
--
作者：
Hu，Xifeng;Chen，Zheng;Wu，Huansheng
传染性法氏囊病病毒 (IBDV) 聚合酶 VP1 蛋白负责转录、初始翻译和病毒基因组复制。关于 VP1 新型翻译后修饰的知识支持鉴定抗病毒新药。由于已知精氨酸残基会被蛋白质精氨酸甲基转移酶 (PRMT) 甲基化，因此我们研究了 IBDV VP1 是否是已知 PRMT 的底物。在这项研究中，我们发现 VP1 与 PRMT5 的精氨酸 426 (R426) 残基特异性相关并被 PRMT5 甲基化。 IBDV 感染导致 PRMT5 在细胞质中积聚，与 VP1 共定位为点状结构。此外，PRMT5的异位表达显着增强了病毒复制。在存在 PMRT5、酶抑制剂和敲除 PRMT5 的情况下，病毒复制显着减少。当R426突变为丙氨酸时，VP1的聚合酶活性被严重破坏，导致病毒复制受损。我们的研究报告了 VP1 的一种新型翻译后修饰，支持其聚合酶功能以促进病毒复制。重要性传染性法氏囊病病毒 (IBDV) VP1 的翻译后修饰对于调节其聚合酶活性非常重要。研究 VP1 特异性修饰的重要性可以更好地了解病毒复制，也可能有助于确定抗病毒化合物的新靶点。我们的工作展示了 PRMT5 介导的 VP1 甲基化的分子机制，这对于病毒聚合酶活性以及病毒复制至关重要。我们的研究扩展了对 VP1 精氨酸甲基化功能的新见解，这可能有助于限制 IBDV 的复制。
The infectious bursal diseases virus (IBDV) polymerase, VP1 protein, is responsible for transcription, initial translation and viral genomic replication. Knowledge about the new kind of post-translational modification of VP1 supports identification of novel drugs against the virus. Because the arginine residue is known to be methylated by protein arginine methyltransferase (PRMT) enzyme, we investigated whether IBDV VP1 is a substrate for known PRMTs. In this study, we show that VP1 is specifically associated with and methylated by PRMT5 at the arginine 426 (R426) residue. IBDV infection causes the accumulation of PRMT5 in the cytoplasm, which colocalizes with VP1 as a punctate structure. In addition, ectopic expression of PRMT5 significantly enhances the viral replication. In the presence of PMRT5, enzyme inhibitor and knockout of PRMT5 remarkably decreased viral replication. The polymerase activity of VP1 was severely damaged when R426 mutated to alanine, resulting in impaired viral replication. Our study reports a novel form of post-translational modification of VP1, which supports its polymerase function to facilitate the viral replication.IMPORTANCEPost-translational modification of infectious bursal disease virus (IBDV) VP1 is important for the regulation of its polymerase activity. Investigation of the significance of specific modification of VP1 can lead to better understanding of viral replication and can probably also help in identifying novel targets for antiviral compounds. Our work demonstrates the molecular mechanism of VP1 methylation mediated by PRMT5, which is critical for viral polymerase activity, as well as viral replication. Our study expands a novel insight into the function of arginine methylation of VP1, which might be useful for limiting the replication of IBDV.