ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cytomegalovirus-mediated activation of pyrimidine biosynthesis drives UDP-sugar synthesis to support viral protein glycosylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Carbohydrates Metabolic Signatures in Immune Cells: Response to Infection.Frontiers in immunology · 2022Pooled it
- Enhanced lactose utilization from milk enriched in Uridine-5'-monophosphate drives hepatic energy storage in young mammals.Food chemistry. Molecular sciences · 2026Article
- Japanese encephalitis virus reprograms host pyrimidine metabolism to facilitate viral replication.Infectious medicine · 2026Article
- Metabolomic Analysis of Lytic KSHV Infection: Induced Host Nucleotide Metabolism Is Required for Infectious Virus Production.Viruses · 2026Article
- Glutamine supports human cytomegalovirus induced lipidome remodeling through reductive carboxylation.PLoS pathogens · 2026Article
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
- HCMV infection depends on EGLN1-mediated mitochondrial activation to increase dNTP pools for viral DNA replication.Cell reports · 2026Article
- Glutamine supports human cytomegalovirus induced lipidome remodeling through reductive carboxylation.bioRxiv : the preprint server for biology · 2026Article
- Metabolic reprogramming induced by CRP deficiency or human CRP transgenic in influenza-infected mice.Frontiers in immunology · 2026Article
- Human cytomegalovirus promotesJournal of virology · 2025Article
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- Human cytomegalovirus promotesbioRxiv : the preprint server for biology · 2025Article
- Vaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction.Journal of virology · 2025Article
- Platelet Ido1 expression is induced during Plasmodium yoelii infection, altering plasma tryptophan metabolites.Blood advances · 2024Article
- Glucose-independent human cytomegalovirus replication is supported by metabolites that feed upper glycolytic branches.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Metabolomic alterations in the plasma of patients with various clinical manifestations of COVID-19.Virology journal · 2024Article
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- Multi-omics analysis reveals the impact of influenza a virus host adaptation on immune signatures in pig tracheal tissue.Frontiers in immunology · 2024Article
- Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.Anti-cancer agents in medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (HCMV) induces numerous changes to the host metabolic network that are critical for high-titer viral replication. We find that HCMV infection substantially induces de novo pyrimidine biosynthetic flux. This activation is important for HCMV replication because inhibition of pyrimidine biosynthetic enzymes substantially decreases the production of infectious virus, which can be rescued through medium supplementation with pyrimidine biosynthetic intermediates. Metabolomic analysis revealed that pyrimidine biosynthetic inhibition considerably reduces the levels of various UDP-sugar metabolites in HCMV-infected, but not mock-infected, cells. Further, UDP-sugar biosynthesis, which provides the sugar substrates required for glycosylation reactions, was found to be induced during HCMV infection. Pyrimidine biosynthetic inhibition also attenuated the glycosylation of the envelope glycoprotein B (gB). Both glycosylation of gB and viral growth were restored by medium supplementation with either UDP-sugar metabolites or pyrimidine precursors. These results indicate that HCMV drives de novo-synthesized pyrimidines to UDP-sugar biosynthesis to support virion protein glycosylation. The importance of this link between pyrimidine biosynthesis and UDP-sugars appears to be partially shared among diverse virus families, because UDP-sugar metabolites rescued the growth attenuation associated with pyrimidine biosynthetic inhibition during influenza A and vesicular stomatitis virus infection, but not murine hepatitis virus infection. In total, our results indicate that viruses can specifically modulate pyrimidine metabolic flux to provide the glycosyl subunits required for protein glycosylation and production of high titers of infectious progeny.
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