Li Xiaolu, Kabza Adam, Ives Ashley N, Thiel Julianne, Waters Katrina M, Qian Wei-Jun, Sims Amy C, Zhang Tong
Biological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United States.
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, United States.
Front Immunol. 2025 May 30;16:1587106. doi: 10.3389/fimmu.2025.1587106. eCollection 2025.
Post-translational modifications (PTMs) are biochemical modifications that can significantly alter protein structure, function, stability, localization, and interactions with other molecules, thereby activating or inactivating intracellular processes. A growing body of research has begun to highlight the role of PTMs, including phosphorylation, ubiquitination, acetylation, and redox modifications, during virus-host interactions. Collectively, these PTMs regulate key steps in mounting the host immune response and control critical host pathways required for productive viral replication. This has led to the conception of antiviral therapeutics that focus on controlling host protein PTMs, potentially offering pathogen-agnostic treatment options and revolutionizing our capacity to prevent virus transmission. On the other hand, viruses can hijack the host cellular PTM machinery to modify viral proteins in promoting viral replication and evading immune surveillance. PTM regulation during virus-host interactions is complex and poorly mapped, and the development of effective PTM-targeted antiviral drugs will require a more comprehensive understanding of the cellular pathways essential for virus replication. In this review, we discuss the roles of PTMs in virus infection and how technological advances in mass spectrometry-based proteomics can capture systems-level PTM changes during viral infection. Additionally, we explore how such knowledge is leveraged to identify PTM-targeted candidates for developing antiviral drugs. Looking ahead, studies focusing on the discovery and functional elucidation of PTMs, either on the host or viral proteins, will not only deepen our understanding of molecular pathology but also pave the way for developing better drugs to fight emerging viruses.
翻译后修饰（PTMs）是一种生物化学修饰，可显著改变蛋白质的结构、功能、稳定性、定位以及与其他分子的相互作用，从而激活或失活细胞内过程。越来越多的研究开始强调PTMs在病毒-宿主相互作用过程中的作用，包括磷酸化、泛素化、乙酰化和氧化还原修饰。总体而言，这些PTMs调节宿主免疫反应的关键步骤，并控制病毒有效复制所需的关键宿主途径。这催生了专注于控制宿主蛋白PTMs的抗病毒疗法概念，可能提供与病原体无关的治疗选择，并彻底改变我们预防病毒传播的能力。另一方面，病毒可以劫持宿主细胞的PTM机制来修饰病毒蛋白，以促进病毒复制并逃避免疫监视。病毒-宿主相互作用过程中的PTM调节复杂且了解不足，开发有效的靶向PTM的抗病毒药物需要更全面地了解病毒复制所必需的细胞途径。在本综述中，我们讨论了PTMs在病毒感染中的作用，以及基于质谱的蛋白质组学技术进展如何捕捉病毒感染期间系统水平的PTM变化。此外，我们探讨了如何利用这些知识来识别用于开发抗病毒药物的靶向PTM的候选物。展望未来，专注于发现和阐明宿主或病毒蛋白上PTMs功能的研究，不仅将加深我们对分子病理学的理解，还将为开发更好的药物来对抗新兴病毒铺平道路。
