ArticlePLoS pathogens2022
Human papillomaviruses sensitize cells to DNA damage induced apoptosis by targeting the innate immune sensor cGAS.
Article in PLoS pathogens, 2022. 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, 35 citations in OpenAlex.
- Differential STING and p53 expression in epidermodysplasia verruciformis-associated versus non-EV cutaneous squamous cell carcinomas.Medical oncology (Northwood, London, England) · 2026Article
- Article
- APOBEC3B regulates HPV replication by inducing R-loop formation and DNA damage.PLoS pathogens · 2026Article
- The radiotherapy induced cyclic GMP-AMP-synthase re-localization and immune signature predicts HNSCC treatment efficacy.Communications medicine · 2026Article
- Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intralesional Immunotherapy for Non-Genital Viral Warts: A Review of Current Evidence and Future Perspectives.International journal of molecular sciences · 2025Review
- The Epithelial Immune Response to Human Papillomavirus Infection.Pathogens (Basel, Switzerland) · 2025Review
- Targeting cGAS-STING pathway for reprogramming tumor-associated macrophages to enhance anti-tumor immunotherapy.Biomarker research · 2025Review
- The role of cGAS-STING signaling in HPV infection and HPV-related cancers.Frontiers in immunology · 2025Review
- The roles of DNA damage repair and innate immune surveillance pathways in HPV pathogenesis.Virology · 2024Review
- EMCV VP2 degrades IFI16 through Caspase-dependent apoptosis to evade IFI16-STING pathway.Virology journal · 2024Article
- Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Article
- The role of HPV11 E7 in modulating STING-dependent interferon β response in recurrent respiratory papillomatosis.Journal of virology · 2024Article
- The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.Cell & bioscience · 2024Review
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- PAD-mediated citrullination is a novel candidate diagnostic marker and druggable target for HPV-associated cervical cancer.Frontiers in cellular and infection microbiology · 2024Article
- The potential role of HPV oncoproteins in the PD-L1/PD-1 pathway in cervical cancer: new perspectives on cervical cancer immunotherapy.Frontiers in oncology · 2024Review
- Oncoproteins E6 and E7 upregulate topoisomerase I to activate the cGAS-PD-L1 pathway in cervical cancer development.Frontiers in pharmacology · 2024Article
- Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions.MedComm · 2023Review
- For Better or Worse: Modulation of the Host DNA Damage Response by Human Papillomavirus.Annual review of virology · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The cyclic GMP-AMP synthase (cGAS) is a critical regulator of the innate immune response acting as a sensor of double-strand DNAs from pathogens or damaged host DNA. Upon activation, cGAS signals through the STING/TBK1/IRF3 pathway to induce interferon expression. Double stranded DNA viruses target the cGAS pathway to facilitate infection. In HPV positive cells that stably maintain viral episomes, the levels of cGAS were found to be significantly increased over those seen in normal human keratinocytes. Furthermore the downstream effectors of the cGAS pathway, STING and IRF3, were fully active in response to signaling from the secondary messenger cGAMP or poly (dA:dT). In HPV positive cells cGAS was detected in both cytoplasmic puncta as well as in DNA damage induced micronuclei. E6 was responsible for increased levels of cGAS that was dependent on inhibition of p53. CRISPR-Cas9 mediated knockout of cGAS prevented activation of STING and IRF3 but had a minimal effect on viral replication. A primary function of cGAS in HPV positive cells was in response to treatment with etoposide or cisplatin which lead to increased levels of H2AX phosphorylation and activation of caspase 3/7 cleavage while having only a minimal effect on activation of homologous recombination repair factors ATM, ATR or CHK2. In HPV positive cells cGAS was found to regulate the levels of the phosphorylated non-homologous end-joining kinase, DNA-PK, which may contribute to H2AX phosphorylation along with other factors. Importantly cGAS was also responsible for increased levels of DNA breaks along with enhanced apoptosis in HPV positive cells but not in HFKs. This study identifies an important and novel role for cGAS in mediating the response of HPV positive cells to chemotherapeutic drugs.
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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 Socratic graph.