DOE OSTI · 3003215
Human Coronavirus-229E Hijacks Key Host-Cell RNA-Processing Complexes for Replication
Abstract
The recent rise in zoonotic coronavirus outbreaks underscores the urgency to understand virus-host interactions and develop potent antiviral therapeutics. Systems biology approaches, particularly proteomics have been invaluable in providing a global overview of such interactions. However, these conventional approaches rely on measuring protein abundance changes which don’t reflect functional shifts. In this study, we employed a high-throughput structural proteomics approach called limited proteolysis-based mass spectrometry (LiP-MS) to capture conformational changes, which we demonstrate are better proxies for functional alterations. We applied this tool to both immortalized and primary human lung cells following human coronavirus 229E (HCoV-229E) infection. We identified significant infection-induced structural changes within RNA processing complexes such as the spliceosome-C and NOP56-associated complex. These observations emphasize that HCoV-229E infection propagates a multi-pronged effort to obstruct the house keeping RNA processing functions in the host. Finally, we show that HCoV-229E replication can be attenuated by the targeted disruption of these complexes, indicating that the identified cellular factories are viable targets to prevent coronavirus infection.
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Sarkar, Snigdha [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)] (ORCID:0000000345510314), Feng, Song [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)] (ORCID:0000000339839009), Mitchell, Hugh D. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)], Berger, Madelyn R. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)], Zhang, Tong [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)] (ORCID:0000000325402017), Attah, Isaac K. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)] (ORCID:0000000296262069), Hutchinson-Bunch, Chelsea M. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)] (ORCID:0000000241843085), Prozapas, Victoria N. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)], Engbrecht, Kristin [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)], King, Stephanie [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)], Sims, Amy C. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Univ. of Washington, Seattle, WA (United States)], Melchior, John T. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Univ. of Cincinnati, OH (United States); Oregon Health and Science Univ., Portland, OR (United States)] (ORCID:0000000337812566). 2025-09-12. Human Coronavirus-229E Hijacks Key Host-Cell RNA-Processing Complexes for Replication. https://doi.org/10.1021/acs.jproteome.5c00400
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