ArticleJournal of virology2012
Varicella-Zoster virus ORF12 protein triggers phosphorylation of ERK1/2 and inhibits apoptosis.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
36 citing papers in PubMed, 57 citations in OpenAlex.
- The prenylated pUS2 protein of pseudorabies virus contributes to phosphorylation of connexin 43 and suppression of gap junctional intercellular communication.Journal of virology · 2026Article
- The ASFV CD2v protein inhibits apoptosis by inducing proteasomal degradation of BimJournal of virology · 2026Article
- Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis, Treatment, and Prevention.MedComm · 2026Review
- Divergent Strategies in Innate Immune Evasion: A Comparative Review of Three Alphaherpesvirus Subfamily Members-PRV, HSV-1, and VZV.Transboundary and emerging diseases · 2026Review
- Kinases Associated with Herpes Zoster Virus Infection Unveiled by Phosphoromics Profiling.Infection and drug resistance · 2025Article
- Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.CNS neuroscience & therapeutics · 2024Review
- Modulation of Apoptosis and Cell Death Pathways by Varicella-Zoster Virus.Current topics in microbiology and immunology · 2023Review
- Sophoridine Suppresses Herpes Simplex Virus Type 1 Infection by Blocking the Activation of Cellular PI3K/Akt and p38 MAPK Pathways.Frontiers in microbiology · 2022Article
- Mitochondria as a Cellular Hub in Infection and Inflammation.International journal of molecular sciences · 2021Review
- The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice.Frontiers in pharmacology · 2021Article
- CircRNA8220 Sponges MiR-8516 to Regulate Cell Viability and Milk Synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR Pathways in Goat Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2020Article
- Manipulation of the Innate Immune Response by Varicella Zoster Virus.Frontiers in immunology · 2020Review
- Functional paralysis of human natural killer cells by alphaherpesviruses.PLoS pathogens · 2019Article
- Potential Anti-Inflammatory and Anti-Cancer Properties of Farnesol.Molecules (Basel, Switzerland) · 2018Review
- Newcastle Disease Virus V Protein Promotes Viral Replication in HeLa Cells through the Activation of MEK/ERK Signaling.Viruses · 2018Article
- Varicella-Zoster Virus ORF63 Protects Human Neuronal and Keratinocyte Cell Lines from Apoptosis and Changes Its Localization upon Apoptosis Induction.Journal of virology · 2018Article
- Oncoprotein Stathmin Modulates Sensitivity to Apoptosis in Hepatocellular Carcinoma Cells During Hepatitis C Viral Replication.Journal of cell death · 2018Article
- Viral strategies for triggering and manipulating mitophagy.Autophagy · 2018Article
- Targeted Genome Sequencing Reveals Varicella-Zoster Virus Open Reading Frame 12 Deletion.Journal of virology · 2017Article
- The ERK-1 function is required for HSV-1-mediated G1/S progression in HEP-2 cells and contributes to virus growth.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mitogen-activated protein kinases (MAPKs) are a family of serine-threonine protein kinases involved in many cellular processes, including cell proliferation, differentiation, inflammation, and cell death. Activation of several MAPKs, including extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK), results in stimulation of activator protein 1 (AP-1), which promotes gene transcription. Previous studies have demonstrated that varicella-zoster virus (VZV) infection activates ERK1/2, p38, and JNK to promote viral replication, but the underlying mechanism(s) is unclear. To identify viral proteins responsible for the activation of MAPK, we used a proteomic approach to screen viral proteins for AP-1 promoter activation by an AP-1-luciferase reporter assay. We found that VZV ORF12 protein, located in the tegument of virions, enhances AP-1 reporter activity. This effect of ORF12 protein was markedly inhibited by a MAPK/ERK kinase 1 and 2 (MEK1/2) inhibitor (U0126), partially blocked by a p38 inhibitor (SB202190), but not inhibited by a JNK inhibitor (SP600125). Expression of VZV ORF12 protein in cells resulted in phosphorylation of ERK1/2 and p38 but not JNK. Infection of cells with a VZV ORF12 deletion mutant resulted in reduced levels of phosphorylated ERK1/2 (p-ERK1/2) compared to infection with wild-type VZV. Furthermore, deletion of ORF12 rendered VZV-infected cells more susceptible to staurosporine-induced apoptosis. In conclusion, VZV ORF12 protein activates the AP-1 pathway by selectively triggering the phosphorylation of ERK1/2 and p38. Cells infected with a VZV ORF12 deletion mutant have reduced levels of p-ERK1/2 and are more susceptible to apoptosis than cells infected with wild-type VZV.
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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.