The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain-containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus lifecycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW domain interactions that could be used as antiviral therapeutics.

中文翻译：

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病毒是模块化的。

WW 结构域是一种模块化蛋白质结构，可识别特定靶蛋白中含有的富含脯氨酸的 Pro-Pro-x-Tyr (PPxY) 基序。WW 结构域的紧凑模块化特性使其非常适合介导复杂网络中的蛋白质与细胞信号通路（例如 Hippo 通路）之间的相互作用。因此，WW 域在过多的正常和疾病过程中都发挥着关键作用。有趣的是，RNA 和 DNA 病毒已经进化出劫持细胞 WW 结构域蛋白质的策略，从而利用这些宿主蛋白质的模块化功能进行病毒生命周期的各个步骤，包括进入、复制和出口。在这篇综述中，我们总结了这个快速扩展领域的主要发现，其中不断发现新的病毒-宿主相互作用。进一步解开这些关键病毒-宿主相互作用的分子方面将继续增强我们对这些病毒的生物学和发病机制的基本理解。我们预计对这些相互作用的更多见解将有助于支持开发一类新型病毒 PPxY-宿主 WW 域相互作用的小分子抑制剂的策略，该抑制剂可用作抗病毒治疗剂。