ArticleScience advances2020
Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection.
Article in Science advances, 2020. 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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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Convergent evolution of viral nucleases targeting cyclic dinucleotides.PLoS pathogens · 2026Review
- APOBEC3-driven attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor.Nature communications · 2026Article
- Engineered fluorescence for live diagnostics and quantification of poxvirus infection.The Journal of general virology · 2026Article
- Molecular mechanism of 2',3'-cGAMP degradation by monkeypox virus poxin-schlafen protein.The Journal of biological chemistry · 2026Article
- Monkeypox virus protein OPG188 antagonizes cGAS-STING antiviral signaling pathway to mediate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhancement of NK cell activity via DNA-sensing inhibition by Poxin transgene.Journal of advanced research · 2026Article
- Mpox virus poxin-schlafen fusion protein suppresses innate antiviral response by sequestering STAT2.Emerging microbes & infections · 2025Article
- Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes.Genome biology and evolution · 2025Article
- A new attenuated and highly immunogenic orthopoxvirus vaccine protects against mpox in mice and macaques.NPJ vaccines · 2025Article
- Review
- Poxin-deficient poxviruses are sensed by cGAS prior to genome replication.The Journal of general virology · 2024Article
- The monkeypox virus-host interplays.Cell insight · 2024Review
- The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses.Nature communications · 2023Article
- CBASS to cGAS-STING: The Origins and Mechanisms of Nucleotide Second Messenger Immune Signaling.Annual review of virology · 2023Review
- Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease.Cancer gene therapy · 2023Article
- Resistance To Poxvirus Lethality Does Not Require the Necroptosis Proteins RIPK3 or MLKL.Journal of virology · 2023Article
- Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis.Viruses · 2023Review
- Role of cytokines in poxvirus host tropism and adaptation.Current opinion in virology · 2022Review
- Poxviruses and the immune system: Implications for monkeypox virus.International immunopharmacology · 2022Review
- Myxoma virus lacking the host range determinant M062 stimulates cGAS-dependent type 1 interferon response and unique transcriptomic changes in human monocytes/macrophages.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Cells contain numerous immune sensors to detect virus infection. The cyclic GMP-AMP (cGAMP) synthase (cGAS) recognizes cytosolic DNA and activates innate immune responses via stimulator of interferon genes (STING), but the impact of DNA sensing pathways on host protective responses has not been fully defined. We demonstrate that cGAS/STING activation is required to resist lethal poxvirus infection. We identified viral Schlafen (vSlfn) as the main STING inhibitor, and ectromelia virus was severely attenuated in the absence of vSlfn. Both vSlfn-mediated virulence and STING inhibitory activity were mapped to the recently discovered poxin cGAMP nuclease domain. Animals were protected from subcutaneous, respiratory, and intravenous infection in the absence of vSlfn, and interferon was the main antiviral protective mechanism controlled by the DNA sensing pathway. Our findings support the idea that manipulation of DNA sensing is an efficient therapeutic strategy in diseases triggered by viral infection or tissue damage-mediated release of self-DNA.
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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.