Cheng Qian, Zhu Siqi, Lv Yanrong, Liu JiongJiong, Su Qinglin, Yuan Meijin, Liu Yang, Yang Kai
State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, China.
School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR 999077, China.
Nucleic Acids Res. 2025 Jun 6;53(11). doi: 10.1093/nar/gkaf506.
Viral DNA-binding proteins, a type of protamine-like protein, pack the viral genome and promote late viral gene expression. In baculovirus Autographa californica multiple nucleopolyhedrovirus, DNA-binding protein P6.9 plays a crucial role in the production of progeny viruses. Earlier studies suggested the importance of P6.9 phosphorylation states in its function, while the detailed mechanism remains elusive. Here, we demonstrated that permanent hypo- and hyper-phosphorylation on the N-terminus of viral P6.9 significantly inhibits the proliferation of progeny viruses. Our data revealed that phosphorylation changes the DNA binding affinity of P6.9, which determines the distinct localization of P6.9 in the host nucleus. Both viral and host gene expressions were largely up or downregulated by the phosphorylation states of P6.9, indicating the central role of P6.9 in governing the tempo of viral replication. Our work provides an intriguing model of how the phosphorylation/dephosphorylation dynamics of P6.9 regulate viral packaging and gene expression patterns, which sheds light on the general principle of viral-host interaction.
病毒DNA结合蛋白是一种鱼精蛋白样蛋白，它包装病毒基因组并促进病毒晚期基因表达。在苜蓿银纹夜蛾多核型多角体病毒中，DNA结合蛋白P6.9在子代病毒的产生中起关键作用。早期研究表明P6.9的磷酸化状态在其功能中很重要，但其详细机制仍不清楚。在这里，我们证明了病毒P6.9 N端的永久性低磷酸化和高磷酸化显著抑制子代病毒的增殖。我们的数据表明，磷酸化改变了P6.9的DNA结合亲和力，这决定了P6.9在宿主细胞核中的不同定位。病毒和宿主基因的表达在很大程度上受P6.9磷酸化状态的上调或下调，这表明P6.9在控制病毒复制节奏中起核心作用。我们的工作提供了一个有趣的模型，说明P6.9的磷酸化/去磷酸化动态如何调节病毒包装和基因表达模式，这为病毒-宿主相互作用的一般原则提供了线索。
