Orally acquired cyclic dinucleotides drive dSTING-dependent antiviral immunity in enterocytes

Segrist, Elisha; Dittmar, Mark; Gold, Beth; Cherry, Sara

doi:10.1016/j.celrep.2021.110150

Cited by 14 publications

(14 citation statements)

References 53 publications

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“…Besides its intracellular role, 2′3′-cGAMP also exists as a soluble, extracellular immunotransmitter [22][23][24] . Therefore, it is possible that apart from being the melanization inhibitor in insects, the secretory P26/poxin homologs might also be involved in degrading extracellular 2′3′-cGAMP in mammals and insects (Fig.…”

Section: Discussionmentioning

confidence: 99%

Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity

et al. 2022

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P26, a homolog of the viral-encoded nuclease poxin that neutralizes the cGAS-STING innate immunity, is widely distributed in various invertebrate viruses, lepidopteran insects, and parasitoid wasps. P26/poxin from certain insect viruses also retains protease activity, though its biological role remains unknown. Given that many P26s contain a signal peptide, it is surmised that P26 may possess certain extracellular functions. Here, we report that a secretory baculoviral P26 suppresses melanization, a prominent insect innate immunity against pathogen invasion. P26 targets the cofactor of a prophenoloxidase-activating protease, and its inhibitory function is independent of nuclease activity. The analysis of P26/poxin homologs from different origins suggests that the ability to inhibit the extracellular melanization pathway is limited to P26s with a signal peptide and not shared by the homologs without it. These findings highlight the independent evolution of a single viral suppressor to perform dual roles in modulating immunity during virus-host adaptation.

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Section: Discussionmentioning

confidence: 99%

Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity

et al. 2022

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“…The discovery of the important role played by the Stimulator of interferon genes (STING) pathway in the antiviral defence of D. melanogaster opens new perspectives [32]. Indeed, STING-dependent signalling can be activated in vivo by injection of cyclic dinucleotides [33][34][35][36]. This provides a powerful means to trigger antiviral immunity in a range of insects, paving the way for evo-immuno (figure 1).…”

Section: Evolutionary Immunology To Delve Into the Biodiversity Of An...mentioning

confidence: 99%

Evolutionary immunology to explore original antiviral strategies

Imler,

Cai,

Meignin

et al. 2024

Phil. Trans. R. Soc. B

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Over the past 25 years, the field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on the developmental mechanisms underlying the evolution of morphological diversity of animals. Evo–devo exploits the key insight that conserved toolkits of development (e.g. Hox genes) are used in animals to produce genetic novelties that provide adaptation to a new environment. Like development, immunity is forged by interactions with the environment, namely the microbial world. Yet, when it comes to the study of immune defence mechanisms in invertebrates, interest primarily focuses on evolutionarily conserved molecules also present in humans. Here, focusing on antiviral immunity, we argue that immune genes not conserved in humans represent an unexplored resource for the discovery of new antiviral strategies. We review recent findings on the cGAS-STING pathway and explain how cyclic dinucleotides produced by cGAS-like receptors may be used to investigate the portfolio of antiviral genes in a broad range of species. This will set the stage for evo–immuno approaches, exploiting the investment in antiviral defences made by metazoans over hundreds of millions of years of evolution. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.

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“…Knockout experiments have provided evidence that DmSTING exerts its antiviral activity through an NF‐κB‐dependent mechanism, specifically involving the transcription factor Relish 28,39 . Similarly, BmSTING, a STING homolog in Bombyx mori , also presents NF‐κB‐dependent antiviral signaling upon nucleopolyhedrovirus (NPV) infection.…”

Section: Primary Antiviral Activity Of the Cgas–sting Pathway From An...mentioning

confidence: 99%

“…Previous studies have shown that Drosophila STING (DmSTING) is capable of activating the immune response upon CDN stimulation. 38,39 Recently, a series of studies have further identified two cGLRs in Drosophila as cGAS homologs to detect nucleic acids and synthesize divergent second messengers, including 3′2′-cGAMP, 2′3′-cGAMP, 2′3′-c-di-GMP, and 2′3′-c-di-AMP. 34,40,41 DmSTING recognizes these second messengers, although its specific preferences remain unidentified, and ultimately exhibits antiviral activity.…”

Section: Primary Antiviral Activity Of the Cgas-sting Pathway From An...mentioning

confidence: 99%

cGAS–STING‐mediated novel nonclassic antiviral activities

Hu,

Ye,

et al. 2024

Journal of Medical Virology

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Stimulatorof interferon genes (STING) is an intracellular sensor of cyclic dinucleotides involved in the innate immune response against pathogen‐ or self‐derived DNA. For years, interferon (IFN) induction of cyclic GMP–AMP synthase (cGAS)–STING has been considered as a canonical pattern defending the host from viral invasion. The mechanism of the cGAS–STING–IFN pathway has been well‐illustrated. However, other signalling cascades driven by cGAS–STING have emerged in recent years and some of them have been found to possess antiviral ability independent of IFN. Here, we summarize the current progress on cGAS–STING‐mediated nonclassic antiviral activities with an emphasis on the nuclear factor‐κB and autophagy pathways, which are the most‐studied pathways. In addition, we briefly present the primordial function of the cGAS–STING pathway in primitive species to show the importance of IFN‐unrelated antiviral activity from an evolutionary angle. Finally, we discuss open questions that need to be solved for further exploitation of this field.

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Orally acquired cyclic dinucleotides drive dSTING-dependent antiviral immunity in enterocytes

Cited by 14 publications

References 53 publications

Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity

Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity

Evolutionary immunology to explore original antiviral strategies

cGAS–STING‐mediated novel nonclassic antiviral activities

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