Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets
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 highligh...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587106/full |
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| author | Xiaolu Li Adam Kabza Ashley N. Ives Julianne Thiel Katrina M. Waters Wei-Jun Qian Amy C. Sims Tong Zhang |
| author_facet | Xiaolu Li Adam Kabza Ashley N. Ives Julianne Thiel Katrina M. Waters Wei-Jun Qian Amy C. Sims Tong Zhang |
| author_sort | Xiaolu Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e31242314a344b2794965763bdf88eeb |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-e31242314a344b2794965763bdf88eeb2025-08-20T03:03:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15871061587106Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targetsXiaolu Li0Adam Kabza1Ashley N. Ives2Julianne Thiel3Katrina M. Waters4Wei-Jun Qian5Amy C. Sims6Tong Zhang7Biological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesBiological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesHanford High School, Richland, WA, United StatesBiological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesBiological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesNuclear Chemical & Biological Technologies Division, Pacific Northwest National Laboratory, Richland, WA, United StatesBiological Sciences Division, Pacific Northwest National Laboratory, Pacific Northwest National Laboratory, Richland, WA, United StatesPost-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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587106/fullPTMsviral infectionantiviral drugproteomephosphorylationredox |
| spellingShingle | Xiaolu Li Adam Kabza Ashley N. Ives Julianne Thiel Katrina M. Waters Wei-Jun Qian Amy C. Sims Tong Zhang Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets Frontiers in Immunology PTMs viral infection antiviral drug proteome phosphorylation redox |
| title | Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| title_full | Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| title_fullStr | Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| title_full_unstemmed | Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| title_short | Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| title_sort | proteome wide characterization of ptms reveals host cell responses to viral infection and identifies putative antiviral drug targets |
| topic | PTMs viral infection antiviral drug proteome phosphorylation redox |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587106/full |
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