Conserved strategies for pathogen evasion of cGAS–STING immunity

Eaglesham, J.B.; Kranzusch, Philip J.

doi:10.1016/j.coi.2020.04.002

Cited by 63 publications

(54 citation statements)

References 71 publications

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“…Moreover, in their latest work, they discovered that DTMUV NS2A competes with duck TBK1 (duTBK1) to bind with duSTING, thus disrupting duSTING dimerization and inhibiting downstream IFN production [88]. The work they performed using an avian model will undoubtedly inform the work we do in mammalian systems in the future and could potentially provide evidence for a conserved pan-flavivirus strategy of modulating host innate immune space by targeting the cGAS/STING pathway [138,139].…”

Section: Duck Tembusu Virusmentioning

confidence: 96%

Innate Immune DNA Sensing of Flaviviruses

Zhu

Fernández-Sesma

2020

Viruses

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Flaviviruses are arthropod-borne RNA viruses that have been used extensively to study host antiviral responses. Often selected just to represent standard single-stranded positive-sense RNA viruses in early studies, the Flavivirus genus over time has taught us how truly unique it is in its remarkable ability to target not just the RNA sensory pathways but also the cytosolic DNA sensing system for its successful replication inside the host cell. This review summarizes the main developments on the unexpected antagonistic strategies utilized by different flaviviruses, with RNA genomes, against the host cyclic GAMP synthase (cGAS)/stimulator of interferon genes (STING) cytosolic DNA sensing pathway in mammalian systems. On the basis of the recent advancements on this topic, we hypothesize that the mechanisms of viral sensing and innate immunity are much more fluid than what we had anticipated, and both viral and host factors will continue to be found as important factors contributing to the host innate immune system in the future.

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Section: Duck Tembusu Virusmentioning

confidence: 96%

Innate Immune DNA Sensing of Flaviviruses

Zhu

Fernández-Sesma

2020

Viruses

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“…A bulk of studies have exhaustively summarized the role of cGAS/STING pathway in regulating antipathogenic and antitumor responses and the adaptive changes of cancerous cells and pathogens to escape cGAS supervision [8,[81][82][83][84]. As we explore and know more about this pathway, we are able to find more in other aspects.…”

Section: Roles Of the Cgas/sting Pathway In Physiological Regulatory mentioning

confidence: 99%

cGAS/STING: novel perspectives of the classic pathway

Gao

Tang

et al. 2020

Mol Biomed

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Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor and innate immune response initiator. Binding with exogenous or endogenous nucleic acids, cGAS activates its downstream adaptor, stimulator of interferon genes (STING). STING then triggers protective immune to enable the elimination of the pathogens and the clearance of cancerous cells. Apparently, aberrantly activated by self-DNA, cGAS/STING pathway is threatening to cause autoimmune and inflammatory diseases. The effects of cGAS/STING in defenses against infection and autoimmune diseases have been well studied, still it is worthwhile to discuss the roles of cGAS/STING pathway beyond the “classical” realm of innate immunity. Recent studies have revealed its involvement in non-canonical inflammasome formation, calcium hemostasis regulation, endoplasmic reticulum (ER) stress response, perception of leaking mitochondrial DNA (mtDNA), autophagy induction, cellular senescence and senescence-associated secretory phenotype (SASP) production, providing an exciting area for future exploration. Previous studies generally focused on the function of cGAS/STING pathway in cytoplasm and immune response. In this review, we summarize the latest research of this pathway on the regulation of other physiological process and STING independent reactions to DNA in micronuclei and nuclei. Together, these studies provide a new perspective of cGAS/STING pathway in human diseases.

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“…Although its role in response to DNA virus infection has been well deciphered (Eaglesham and Kranzusch, 2020), the role of cGAS/STING against RNA viruses such as paramyxoviruses is poorly understood. While cGAS was reported to interact with dsRNA, no production of cGAMP was detected, thus cGAS could not canonically activate STING directly (Civril et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Activation of cGAS/STING pathway upon paramyxovirus infection

Iampietro

Dumont

Mathieu

et al. 2020

Preprint

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SUMMARYDuring inflammatory diseases, cancer and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV) and Measles virus (MeV), can also trigger the cGAS/STING axis. While mice deficient for MyD88, TRIF and MAVS still moderately control NiV infection when compared to WT mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type-I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection, and possibly represent attractive targets to develop countermeasures against severe disease induced by these pathogens.

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Conserved strategies for pathogen evasion of cGAS–STING immunity

Cited by 63 publications

References 71 publications

Innate Immune DNA Sensing of Flaviviruses

Innate Immune DNA Sensing of Flaviviruses

cGAS/STING: novel perspectives of the classic pathway

Activation of cGAS/STING pathway upon paramyxovirus infection

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