ArticlePLoS pathogens2009
De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 217 citations in OpenAlex.
- Chromatin Regulation of HSV Gene Transcription.Viruses · 2025Review
- Human alpha-herpesvirus 1 (HSV-1) viral replication and reactivation from latency are expedited by the glucocorticoid receptor.Journal of virology · 2025Review
- Co-option of mitochondrial nucleic acid-sensing pathways by HSV-1 UL12.5 for reactivation from latent infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The opportunities and challenges of epigenetic approaches to manage herpes simplex infections.Expert review of anti-infective therapy · 2024Review
- Lytic promoter activity during herpes simplex virus latency is dependent on genome location.Journal of virology · 2024Article
- Neuronal expression of herpes simplex virus-1 VP16 protein induces pseudorabies virus escape from silencing and reactivation.Journal of virology · 2024Article
- Co-option of mitochondrial nucleic acid sensing pathways by HSV-1 UL12.5 for reactivation from latent Infection.bioRxiv : the preprint server for biology · 2024Article
- c-Jun signaling during initial HSV-1 infection modulates latency to enhance later reactivation in addition to directly promoting the progression to full reactivation.Journal of virology · 2024Article
- Advances in the immunoescape mechanisms exploited by alphaherpesviruses.Frontiers in microbiology · 2024Review
- Review
- Intimate Relationship Between Stress and Human Alpha‑Herpes Virus 1 (HSV‑1) Reactivation from Latency.Current clinical microbiology reports · 2023Article
- c-Jun Signaling During Initial HSV-1 Infection Modulates Latency to Enhance Later Reactivation in addition to Directly Promoting the Progression to Full Reactivation.bioRxiv : the preprint server for biology · 2023Article
- The Intersection of Innate Immune Pathways with the Latent Herpes Simplex Virus Genome.Journal of virology · 2023Review
- Host factors associated with either VP16 or VP16-induced complex differentially affect HSV-1 lytic infection.Reviews in medical virology · 2022Review
- Establishing a Herpesvirus Quiescent Infection in Differentiated Human Dorsal Root Ganglion Neuronal Cell Line Mediated by Micro-RNA Overexpression.Pathogens (Basel, Switzerland) · 2022Article
- DLK-Dependent Biphasic Reactivation of Herpes Simplex Virus Latency Established in the Absence of Antivirals.Journal of virology · 2022Article
- Review
- Article
- Probing transient memory of cellular states using single-cell lineages.Frontiers in microbiology · 2022Review
- Pathogenesis and virulence of herpes simplex virus.Virulence · 2021Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
Abstract
The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycle.
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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.