ArticleMolecular cell2019
TOP2β-Dependent Nuclear DNA Damage Shapes Extracellular Growth Factor Responses via Dynamic AKT Phosphorylation to Control Virus Latency.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 40 citations in OpenAlex.
- The Host Cell Factor Phosphatase-2A Subunit PR130 Restricts Replication of Herpes Simplex Virus Type-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- Counteracting FOX proteins epigenetically control the herpesvirus lytic-latent balance.Nature communications · 2026Article
- Article
- 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
- Vistas in Signaling Pathways Implicated in HSV-1 Reactivation.International journal of molecular sciences · 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
- DNA methylation regulates RNA mCell proliferation · 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
- 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
- Article
- Article
- DLK-Dependent Biphasic Reactivation of Herpes Simplex Virus Latency Established in the Absence of Antivirals.Journal of virology · 2022Article
- Article
- Review
- Temporal dynamics of HCMV gene expression in lytic and latent infections.Cell reports · 2022Article
- Single-cell transcriptomics identifies Gadd45b as a regulator of herpesvirus-reactivating neurons.EMBO reports · 2022Article
- Minding the message: tactics controlling RNA decay, modification, and translation in virus-infected cells.Genes & development · 2022Review
- Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity.iScience · 2022Article
- Herpes Simplex Virus 1 Manipulates Host Cell Antiviral and Proviral DNA Damage Responses.mBio · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mTOR pathway integrates both extracellular and intracellular signals and serves as a central regulator of cell metabolism, growth, survival, and stress responses. Neurotropic viruses, such as herpes simplex virus-1 (HSV-1), also rely on cellular AKT-mTORC1 signaling to achieve viral latency. Here, we define a novel genotoxic response whereby spatially separated signals initiated by extracellular neurotrophic factors and nuclear DNA damage are integrated by the AKT-mTORC1 pathway. We demonstrate that endogenous DNA double-strand breaks (DSBs) mediated by Topoisomerase 2β-DNA cleavage complex (TOP2βcc) intermediates are required to achieve AKT-mTORC1 signaling and maintain HSV-1 latency in neurons. Suppression of host DNA-repair pathways that remove TOP2βcc trigger HSV-1 reactivation. Moreover, perturbation of AKT phosphorylation dynamics by downregulating the PHLPP1 phosphatase led to AKT mis-localization and disruption of DSB-induced HSV-1 reactivation. Thus, the cellular genome integrity and environmental inputs are consolidated and co-opted by a latent virus to balance lifelong infection with transmission.
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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.