ArticlePloS one2013
Inhibition of cdk9 during herpes simplex virus 1 infection impedes viral transcription.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.Journal of gynecologic oncology · 2024Trial
- Selective effects of cyclin dependent kinase inhibitors in gammaherpesvirus reactivation from latency.bioRxiv : the preprint server for biology · 2026Article
- Repurposing of CDK Inhibitors as Host Targeting Antivirals: A Mini- Review.Mini reviews in medicinal chemistry · 2025Review
- Herpes simplex virus 1 inhibits phosphorylation of RNA polymerase II CTD serine-7.Journal of virology · 2024Article
- A Revision of Herpes Simplex Virus Type 1 Transcription: First, Repress; Then, Express.Microorganisms · 2024Review
- The Pharmacological Implications of Flavopiridol: An Updated Overview.Molecules (Basel, Switzerland) · 2023Review
- A Recombinant Duck Plague Virus Containing the ICP27 Deletion Marker Provides Robust Protection in Ducks.Microbiology spectrum · 2023Article
- The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.Nature communications · 2023Article
- Cellular state landscape and herpes simplex virus type 1 infection progression are connected.Nature communications · 2023Article
- When cyclin-dependent kinases meet viral infections, including SARS-CoV-2.Journal of medical virology · 2022Review
- ICP22 of Herpes Simplex Virus 1 Decreases RNA Polymerase Processivity.Journal of virology · 2022Article
- HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation.Vaccines · 2021Article
- A Review of the Multipronged Attack of Herpes Simplex Virus 1 on the Host Transcriptional Machinery.Viruses · 2021Review
- Cohesin promotes HSV-1 lytic transcription by facilitating the binding of RNA Pol II on viral genes.Virology journal · 2021Article
- ICP22/IE63 Mediated Transcriptional Regulation and Immune Evasion: Two Important Survival Strategies for Alphaherpesviruses.Frontiers in immunology · 2021Review
- "Non-Essential" Proteins of HSV-1 with Essential Roles In Vivo: A Comprehensive Review.Viruses · 2020Review
- New Insights on Molecular Mechanism of Hepatitis B Virus Covalently Closed Circular DNA Formation.Cells · 2020Review
- RNA Polymerase II Promoter-Proximal Pausing and Release to Elongation Are Key Steps Regulating Herpes Simplex Virus 1 Transcription.Journal of virology · 2020Article
- HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.PLoS pathogens · 2018Article
- A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.mBio · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
During herpes simplex virus 1 (HSV-1) infection there is a loss of the serine-2 phosphorylated form of RNA polymerase II (RNAP II) found in elongation complexes. This occurs in part because RNAP II undergoes ubiquitination and proteasomal degradation during times of highly active viral transcription, which may result from stalled elongating complexes. In addition, a viral protein, ICP22, was reported to trigger a loss of serine-2 RNAP II. These findings have led to some speculation that the serine-2 phosphorylated form of RNAP II may not be required for HSV-1 transcription, although this form is required for cellular transcription elongation and RNA processing. Cellular kinase cdk9 phosphorylates serine-2 in the C-terminal domain (CTD) of RNAP II. To determine if serine-2 phosphorylated RNAP II is required for HSV-1 transcription, we inhibited cdk9 during HSV-1 infection and measured viral gene expression. Inhibition was achieved by adding cdk9 inhibitors 5,6-dichlorobenzimidazone-1-β-D-ribofuranoside (DRB) or flavopiridol (FVP) or by expression of a dominant-negative cdk9 or HEXIM1, which in conjunction with 7SK snRNA inhibits cdk9 in complex with cyclin 1. Here we report that inhibition of cdk9 resulted in decreased viral yields and levels of late proteins, poor formation of viral transcription-replication compartments, reduced levels of poly(A)+ mRNA and decreased RNA synthesis as measured by uptake of 5-bromouridine into nascent RNA. Importantly, a global reduction in viral mRNAs was seen as determined by microarray analysis. We conclude that serine-2 phosphorylation of the CTD of RNAP II is required for HSV-1 transcription.
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Registered trials
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