October 17th 2024

Published in PLoS Pathogens: picornaviruses modulate nucleotide metabolism

Published in PLoS Pathogens: picornaviruses modulate nucleotide metabolism

The CARE partner Utrecht University (UU) assessed the modulation of host metabolism by two picornaviruses using steady state as well as 13C-glucose tracing metabolomics. The family Picornaviridae, a large family of small, non-enveloped viruses with a single stranded positive sense RNA genome, includes many well-known human and animal pathogens. Upon infection of their host, these viruses modulate several cellular processes for efficient replication and spreading, such as host cell gene expression, intracellular protein and membrane transport, and cell death pathways. However, little is known about the effects of picornaviruses on cellular metabolism, an important aspect in virus replication. Indeed, viruses actively reprogram the metabolism of the host to ensure the availability of sufficient building blocks to be able to replicate and spread.

UU showed that both coxsackievirus B3 (CVB3), an enterovirus, and encephalomyocarditis, a cardiovirus, increase the levels of pyrimidine and purine metabolites. This increase is mediated through degradation of nucleic acids and nucleotide recycling, rather than upregulation of de novo synthesis.

Moreover, by integrating the metabolomics data with a previously acquired phosphoproteomics dataset of CVB3-infected cells, UU identified alterations in phosphorylation status of key enzymes involved in nucleotide metabolism, providing insight into the regulation of this during infection.

Insight into picornaviral modulation of cellular metabolism is important to increase our understanding of picornavirus-host interactions and may uncover novel therapeutic strategies. This work was important to establish assays and methodology to evaluate the impact of coronaviruses on host cells in CARE.

To learn more, click here: Modulation of nucleotide metabolism by picornaviruses