ArticleCell research2012
Coxsackievirus mutants that can bypass host factor PI4KIIIβ and the need for high levels of PI4P lipids for replication.
Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 131 citations in OpenAlex.
- Reciprocal control of viral infection and phosphoinositide dynamics.FEBS letters · 2026Review
- Phosphatidylinositol 4-kinase as a target of pathogens-friend or foe?FEBS letters · 2026Review
- Genotype-by-inhibitor interactions to dissect enterovirus replication.Nature communications · 2026Article
- Genotype-by-Inhibitor Interactions to Dissect Enterovirus Replication.Research square · 2025Article
- Cell-based sialoglycan arrays for directly comparing influenza A virus receptor requirements for binding and infection.iScience · 2025Article
- Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections.Infectious disease reports · 2025Review
- Overview of host-directed antiviral targets for future research and drug development.Acta pharmaceutica Sinica. B · 2025Review
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- 4-Trifluoromethyl bithiazoles as broad-spectrum antimicrobial agents for virus-related bacterial infections or co-infections.RSC medicinal chemistry · 2024Article
- Antiviral Mechanisms of Saucerneol fromViruses · 2023Article
- Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ.Microbiology spectrum · 2023Article
- H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Human-type sialic acid receptors contribute to avian influenza A virus binding and entry by hetero-multivalent interactions.Nature communications · 2022Article
- Fighting Enteroviral Infections to Prevent Type 1 Diabetes.Microorganisms · 2022Article
- High-Order Epistasis and Functional Coupling of Infection Steps Drive Virus Evolution toward Independence from a Host Pathway.Microbiology spectrum · 2021Article
- Secretory Carrier Membrane Protein 3 Interacts with 3A Viral Protein of Enterovirus and Participates in Viral Replication.Microbiology spectrum · 2021Article
- Novel capsid binder and PI4KIIIbeta inhibitors for EV-A71 replication inhibition.Scientific reports · 2021Article
- Picornaviruses: A View from 3A.Viruses · 2021Review
- Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. Therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are unlikely to mutate in response to therapy. We recently demonstrated that phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) and its product phosphatidylinositol-4-phosphate (PI4P) are essential for replication of enteroviruses, a group of medically important RNA viruses including poliovirus (PV), coxsackievirus, rhinovirus, and enterovirus 71. Here, we show that enviroxime and GW5074 decreased PI4P levels at the Golgi complex by directly inhibiting PI4KIIIβ. Coxsackievirus mutants resistant to these inhibitors harbor single point mutations in the non-structural protein 3A. These 3A mutations did not confer compound-resistance by restoring the activity of PI4KIIIβ in the presence of the compounds. Instead, replication of the mutant viruses no longer depended on PI4KIIIβ, since their replication was insensitive to siRNA-mediated depletion of PI4KIIIβ. The mutant viruses also did not rely on other isoforms of PI4K. Consistently, no high level of PI4P could be detected at the replication sites induced by the mutant viruses in the presence of the compounds. Collectively, these findings indicate that through specific single point mutations in 3A, CVB3 can bypass an essential host factor and lipid for its propagation, which is a new example of RNA viruses acquiring resistance against antiviral compounds, even when they directly target host factors.
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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.