REVIEW article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1587106
This article is part of the Research TopicThe Impact of Proteomics on Understanding Inflammatory and Infectious DiseasesView all 5 articles
Proteome-Wide Characterization of PTMs to Reveal Host Cell Responses to Viral Infection and Identify Putative Antiviral Drug Targets
Provisionally accepted
Xiaolu Li1
Adam Kabza1Ashley N Ives1
Julianne Thiel2
Katrina M Waters1
Wei-Jun Qian1
Amy C Sims1*
Tong Zhang1*- 1Pacific Northwest National Laboratory (DOE), Richland, United States
- 2Hanford High School, RICHLAND, United States
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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 host/PTM-targeted candidate 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.
Keywords: PTMs, viral infection, antiviral drug, Proteome, Phosphorylation, redox, Ubiquitination, Acetylation
Received: 03 Mar 2025; Accepted: 05 May 2025.
Copyright: © 2025 Li, Kabza, Ives, Thiel, Waters, Qian, Sims and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Amy C Sims, Pacific Northwest National Laboratory (DOE), Richland, United States
Tong Zhang, Pacific Northwest National Laboratory (DOE), Richland, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.