ArticleJournal of virology2013
Herpes simplex virus 1 serine/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 146 citations in OpenAlex.
- Immune Evasion by Neurotropic Viruses: Molecular Strategies, Cellular Targets, and Consequences for CNS Infection.International journal of molecular sciences · 2026Review
- Duck plague virus LORF2 utilizes RNF34 to inhibit antiviral innate immunity by ubiquitination and degradation of IRF7.PLoS pathogens · 2026Article
- HSV-1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance.Journal of medical virology · 2025Review
- Molecular mechanisms of co-infections.EMBO reports · 2025Review
- In the Absence of Type-1 IFN, HSV-1 LAT Increases γ34.5 Expression and Enhances Mortality in Infected Mice.Viruses · 2025Article
- Impact of the changes in substrate specificity of herpes simplex virus 1 protein kinase Us3 on viral infectionJournal of virology · 2025Article
- IFNβ absence compensates for LAT functions in latency reactivation and T cell exhaustion.Journal of virology · 2025Article
- Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Marek's disease virus protein kinase US3 inhibits DNA-sensing antiviral innate immunity via abrogating activation of NF-κB.Microbiology spectrum · 2025Article
- The antiviral activity of myricetin against pseudorabies virus through regulation of the type I interferon signaling pathway.Journal of virology · 2025Article
- Identifying an Abnormal Phosphorylated Adaptor by Viral Kinase Using Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Tug of war: innate immunity and herpes simplex keratitis.Frontiers in immunology · 2025Review
- Post-translational modifications as a key mechanism for herpes simplex virus type I evasion of host innate immunity.Frontiers in microbiology · 2025Review
- A Guideline Strategy for Identifying a Viral Gene/Protein Evading Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A Better Understanding of the Clinical and Pathological Changes in Viral Retinitis: Steps to Improve Visual Outcomes.Microorganisms · 2024Review
- Article
- Viral-bacterial co-infections screen in vitro reveals molecular processes affecting pathogen proliferation and host cell viability.Nature communications · 2024Article
- The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice.PLoS pathogens · 2024Article
- Manganese Exacerbates ConA-Induced Liver Inflammation via the cGAS-STING Signaling Pathway.Inflammation · 2024Article
- HSV1-induced enhancement of productive HIV-1 replication is associated with interferon pathway downregulation in human macrophages.Memorias do Instituto Oswaldo Cruz · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral infection initiates a series of signaling cascades that lead to the transcription of interferons (IFNs), finally inducing interferon-stimulated genes (ISGs) to eliminate viruses. Viruses have evolved a variety of strategies to modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) US3, a Ser/Thr kinase conserved in alphaherpesviruses, was previously reported to counteract host innate immunity; however, the molecular mechanism is elusive. In this study, we report that US3 blocks IFN-β production by hyperphosphorylating IFN regulatory factor 3 (IRF3). Ectopic expression of US3 protein significantly inhibited Sendai virus (SeV)-mediated activation of IFN-β and IFN-stimulated response element (ISRE) promoters and the transcription of IFN-β, ISG54, and ISG56. US3 was also shown to block SeV-induced dimerization and nuclear translocation of IRF3. The kinase activity was indispensable for its inhibitory function, as kinase-dead (KD) US3 mutants K220M and D305A could not inhibit IFN-β production. Furthermore, US3 interacted with and hyperphosphorylated IRF3 at Ser175 to prevent IRF3 activation. Finally, the US3 KD mutant viruses were constructed and denoted K220M or D305A HSV-1, respectively. Cells and mice infected with both mutant viruses produced remarkably larger amounts of IFN-β than those infected with wild-type HSV-1. For the first time, these findings provide convincing evidence that US3 hyperphosphorylates IRF3, blocks the production of IFN-β, and subverts host innate immunity.
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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.