Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection
Summary
Viruses, including picornaviruses, modulate cellular metabolism to generate sufficient building blocks for virus replication and dissemination. Previously, we showed that two picornaviruses, coxsackievirus B3 (CVB3) and EMCV, remodel nucleotide metabolism during infection. Here, we investigated whether this modulation is attributable to specific viral proteins. For this, we studied the modulation of metabolism by several recombinant CVB3 and EMCV viruses in HeLa cells. Using isotope tracing metabolomics with three distinct labels, 13C6-glucose or 13C5/15N2-glutamine, we reveal that the 2A protease of CVB3 and the Leader protein of EMCV inhibit de novo nucleotide synthesis. Furthermore, we show that nucleotide metabolism is also reprogrammed by CVB3 and EMCV in human induced pluripotent stem cell-derived cardiomyocytes. Our insights are important to increase understanding of picornavirus-host interactions and may lead to novel therapeutic strategies. Copyright: © 2025 Nouwen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
| Authors | Nouwen LV, Zaal EA, Buitendijk I, Zwaagstra M, Aloise C, van Vliet ALW, Schipper JG, van Mil A, Berkers CR, van Kuppeveld FJM |
|---|---|
| Journal | PLoS pathogens |
| Publication Date | 2025 Jul;21(7):e1013293 |
| PubMed | 40608831 |
| PubMed Central | PMC12244537 |
| DOI | 10.1371/journal.ppat.1013293 |