ArticlePLoS pathogens2011
An E2F1-mediated DNA damage response contributes to the replication of human cytomegalovirus.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 71 citations in OpenAlex.
- DNA damage responses in HCMV infection: emerging mechanisms and outstanding questions.Journal of virology · 2026Review
- Transcriptional factor ATF3 impairs KSHV lytic replication by suppressing the expression of viral bZIP protein K8.PLoS pathogens · 2026Article
- Human cytomegalovirus regulates host DNA repair machinery for viral genome integrity.Nucleic acids research · 2026Article
- E2F1 suppresses Epstein-Barr virus lytic reactivation through cellular and viral transcriptional networks.PLoS pathogens · 2025Article
- Article
- Complex roles for proliferating cell nuclear antigen in restricting human cytomegalovirus replication.bioRxiv : the preprint server for biology · 2025Article
- Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication.Nature communications · 2024Article
- Human cytomegalovirus infection triggers a paracrine senescence loop in renal epithelial cells.Communications biology · 2024Article
- DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus.Virology journal · 2023Review
- Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair.Trends in microbiology · 2022Review
- Human cytomegalovirus hijacks host stress response fueling replication stress and genome instability.Cell death and differentiation · 2022Article
- Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus.EBioMedicine · 2022Article
- Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection.Viruses · 2021Article
- Human cytomegalovirus-induced host protein citrullination is crucial for viral replication.Nature communications · 2021Article
- Functional regulation of the structure-specific endonuclease FEN1 by the human cytomegalovirus protein IE1 suggests a role for the re-initiation of stalled viral replication forks.PLoS pathogens · 2021Article
- Herpes Simplex Virus 1 Manipulates Host Cell Antiviral and Proviral DNA Damage Responses.mBio · 2021Article
- Importance of miR-UL-148D Expression Pattern in Cytomegalovirus Infected Transplant Patients.International journal of organ transplantation medicine · 2021Article
- Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus.Frontiers in immunology · 2021Article
- HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Murine Cytomegalovirus M25 Proteins Sequester the Tumor Suppressor Protein p53 in Nuclear Accumulations.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses.
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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.