ArticlePLoS pathogens2013
Herpes simplex virus type 1 single strand DNA binding protein and helicase/primase complex disable cellular ATR signaling.
Article in PLoS pathogens, 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, 30 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 damage responses in HCMV infection: emerging mechanisms and outstanding questions.Journal of virology · 2026Review
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- A Guideline Strategy for Identifying a Viral Gene/Protein Evading Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The herpes simplex virus alkaline nuclease is required to maintain replication fork progression.Journal of virology · 2024Article
- DNA Damage Response Differentially Affects BoHV-1 Gene Transcription in Cell Type-Dependent Manners.Biomedicines · 2022Article
- The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1.Microbiology and molecular biology reviews : MMBR · 2020Review
- HSV-1 Hijacks the Host DNA Damage Response in Corneal Epithelial Cells through ICP4-Mediated Activation of ATM.Investigative ophthalmology & visual science · 2020Article
- Four-dimensional analyses show that replication compartments are clonal factories in which Epstein-Barr viral DNA amplification is coordinated.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Early Nuclear Events after Herpesviral Infection.Journal of clinical medicine · 2019Review
- Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3.Journal of virology · 2019Article
- Virus DNA Replication and the Host DNA Damage Response.Annual review of virology · 2018Review
- The ATM and Rad3-Related (ATR) Protein Kinase Pathway Is Activated by Herpes Simplex Virus 1 and Required for Efficient Viral Replication.Journal of virology · 2018Article
- Isolation and Characterization of vΔI3 Confirm that Vaccinia Virus SSB Plays an Essential Role in Viral Replication.Journal of virology · 2018Article
- Article
- Review
- Therapeutic targeting of chemoresistant and recurrent glioblastoma stem cells with a proapoptotic variant of oncolytic herpes simplex virus.International journal of cancer · 2017Article
- CTCF interacts with the lytic HSV-1 genome to promote viral transcription.Scientific reports · 2017Article
- New strategies against drug resistance to herpes simplex virus.International journal of oral science · 2016Review
- H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication.Virology journal · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Herpes Simplex Virus type 1 (HSV-1) has evolved to disable the cellular DNA damage response kinase, ATR. We have previously shown that HSV-1-infected cells are unable to phosphorylate the ATR substrate Chk1, even under conditions in which replication forks are stalled. Here we report that the HSV-1 single stranded DNA binding protein (ICP8), and the helicase/primase complex (UL8/UL5/UL52) form a nuclear complex in transfected cells that is necessary and sufficient to disable ATR signaling. This complex localizes to sites of DNA damage and colocalizes with ATR/ATRIP and RPA, but under these conditions, the Rad9-Rad1-Hus1 checkpoint clamp (9-1-1) do not. ATR is generally activated by substrates that contain ssDNA adjacent to dsDNA, and previous work from our laboratory has shown that ICP8 and helicase/primase also recognize this substrate. We suggest that these four viral proteins prevent ATR activation by binding to the DNA substrate and obstructing loading of the 9-1-1 checkpoint clamp. Exclusion of 9-1-1 prevents recruitment of TopBP1, the ATR kinase activator, and thus effectively disables ATR signaling. These data provide the first example of viral DNA replication proteins obscuring access to a DNA substrate that would normally trigger a DNA damage response and checkpoint signaling. This unusual mechanism used by HSV suggests that it may be possible to inhibit ATR signaling by preventing recruitment of the 9-1-1 clamp and TopBP1.
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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.