ArticleThe Journal of cell biology2012
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed.
- Advances in Antiviral Drug Development Targeting Enteroviruses: From Viral Proteins to Host Factors.Viruses · 2026Review
- Review
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- Virus Infection and mRNA Nuclear Export.International journal of molecular sciences · 2023Review
- Development of a biomarker to monitor target engagement after treatment with dihydroorotate dehydrogenase inhibitors.Biochemical pharmacology · 2022Article
- Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome.mSystems · 2022Article
- Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling.The Journal of clinical investigation · 2022Article
- Enterovirus A71 antivirals: Past, present, and future.Acta pharmaceutica Sinica. B · 2022Article
- Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection.The Journal of biological chemistry · 2021Review
- Structure and Activities of the NS1 Influenza Protein and Progress in the Development of Small-Molecule Drugs.International journal of molecular sciences · 2021Review
- Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression.Science advances · 2021Article
- Molecular mechanism underlying selective inhibition of mRNA nuclear export by herpesvirus protein ORF10.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross.Cell reports · 2020Article
- Alternative Experimental Models for Studying Influenza Proteins, Host-Virus Interactions and Anti-Influenza Drugs.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination.Neuron · 2019Article
- Influenza Virus NS1 Protein-RNA Interactome Reveals Intron Targeting.Journal of virology · 2018Article
- A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle.Genome medicine · 2018Article
- Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication.PLoS pathogens · 2017Article
- Fluorescence assay of dihydroorotate dehydrogenase that may become a cancer biomarker.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
The NS1 protein of influenza virus is a major virulence factor essential for virus replication, as it redirects the host cell to promote viral protein expression. NS1 inhibits cellular messenger ribonucleic acid (mRNA) processing and export, down-regulating host gene expression and enhancing viral gene expression. We report in this paper the identification of a nontoxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of the virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for de novo pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of vesicular stomatitis virus M (matrix) protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.