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DOE OSTI · 3365257

Human Coronavirus 229E Infection Alters Histone Proteoforms

Ives, Ashley N. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division]·Thibert, Stephanie [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division]·Berger, Madelyn R. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division]·Gaffrey, Matthew J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division]·Mitchell, Hugh D. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division]·Williams, Sarai M. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division]·Zhou, Mowei [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000335753224)·Waters, Katrina M. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000346965396)·Sims, Amy C. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Nuclear, Chemical and Biological Technologies Division; University of Washington, Seattle, WA (United States)]·Zhang, Tong [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000325402017)
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Abstract

Viruses rely on host machinery to replicate, and growing evidence demonstrates that they utilize host epigenetic regulation, including histone modification, to modulate host gene expression for their benefit. Herein, we employed top-down proteomics to quantify histone proteoforms in a model human lung cell line following human coronavirus 229E (HCoV-229E) infection and compared them to mock-infected controls. A total of 572 proteoforms from mock-infected and HCoV-229E infected human lung fibroblast (MRC5) cells (N = 5 per condition) were identified; this included 461 histone proteoforms that were assigned to H2A, H2B, H3, or H4. 200 histone proteoforms were quantifiable, and differential abundance analysis revealed several statistically significant changes in both reversible post-translational modifications (e.g. phosphorylation, acetylation) and the truncation states of core histones. Notably, we found decreased abundance of C-terminally truncated histone H2A and N-terminally truncated histone H3 in HCoV-229E-infected samples. These findings underscore the power of top-down proteomics to resolve unique truncation states of proteoforms and support the hypothesis that viruses alter histone length (removing regulatory sites) to influence host gene expression.

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60 APPLIED LIFE SCIENCESHCoV-229 infectionhistoneproteoformstop-down proteomicstruncation

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Ives, Ashley N. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division], Thibert, Stephanie [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division], Berger, Madelyn R. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division], Gaffrey, Matthew J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division], Mitchell, Hugh D. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division], Williams, Sarai M. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Division], Zhou, Mowei [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000335753224), Waters, Katrina M. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000346965396), Sims, Amy C. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Nuclear, Chemical and Biological Technologies Division; University of Washington, Seattle, WA (United States)], Zhang, Tong [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division] (ORCID:0000000325402017). 2026-04-28. Human Coronavirus 229E Infection Alters Histone Proteoforms. https://doi.org/10.1021/acs.jproteome.5c01015

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