Targeting of the cGAS-STING system by DNA viruses

Phelan, Thomas; Little, Mark A.; Brady, Gareth

doi:10.1016/j.bcp.2020.113831

Cited by 29 publications

(29 citation statements)

References 103 publications

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“…cGAS-STING- and TNF-α-induced NF-κB activation contributes to the expression of a variety of proinflammatory cytokines, including IL-1β, TNF-α, and IL-6 during DNA virus infection ( 23 ). F317L inhibited the activation of NF-κB promoter activation; we thus examined whether F317L inhibited the expression of proinflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

Yang

Tian

et al. 2021

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Section: Resultsmentioning

confidence: 99%

African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

Yang

Tian

et al. 2021

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“…Stimulator of interferon genes (STING), also called mediator of IRF3 activation (MITA) or transmembrane protein 173 (TMEM173), was found to be a novel DNA recognition receptor. Since STING was discovered in 2012, an increasing number of studies have confirmed the existence of the cGAS–cGAMP–STING pathway in different conditions and its vital role in the removal of DNA viruses ( 39 , 40 ).…”

Section: Mechanisms Contributing To the Mtdna-associated Pathogenesis Of Akimentioning

confidence: 99%

Circulating Mitochondrial DNA Stimulates Innate Immune Signaling Pathways to Mediate Acute Kidney Injury

Liu

Gong

2021

Front. Immunol.

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Mitochondrial dysfunction is increasingly considered as a critical contributor to the occurrence and progression of acute kidney injury (AKI). However, the mechanisms by which damaged mitochondria mediate AKI progression are multifactorial and complicated. Mitochondrial DNA (mtDNA) released from damaged mitochondria could serve as a danger-associated molecular pattern (DAMP) and activate the innate immune system through STING, TLR9, NLRP3, and some other adaptors, and further mediate tubular cell inflammation and apoptosis. Accumulating evidence has demonstrated the important role of circulating mtDNA and its related pathways in the progression of AKI, and regulating the proteins involved in these pathways may be an effective strategy to reduce renal tubular injury and alleviate AKI. Here, we aim to provide a comprehensive overview of recent studies on mtDNA-mediated renal pathological events to provide new insights in the setting of AKI.

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“…For instance, UL36 can prevent NF-κB activation by cleaving IκBa poly ubiquitin chains while UL46 and ICP27 interact with STING and TBK1 to prevent the activation of IRF3 and interferon stimulated gene (ISG) expression (Christensen et al, 2016 ; Deschamps and Kalamvoki, 2017 ; Ye et al, 2017 ; You et al, 2019 ). Since all members of the family Herpesviridae appear to target cGAS [ Table 2 and as reviewed in Chan and Gack ( 2016 ) and Phelan et al ( 2020 )], and such viruses can cause latent infections, it is tempting to speculate that the inhibition of this sensor may play a critical role in establishing viral latency. Such a mechanism could be of particular importance for HSV encephalitis as the reactivation of a latent infection is thought to be a key contributor to the development of this condition (Menendez and Carr, 2017 ).…”

Section: Cgas/stingmentioning

confidence: 99%

Cytosolic DNA Sensors and CNS Responses to Viral Pathogens

Jeffries

Marriott

2020

Front. Cell. Infect. Microbiol.

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Viral central nervous system (CNS) infections can lead to life threatening encephalitis and long-term neurological deficits in survivors. Resident CNS cell types, such as astrocytes and microglia, are known to produce key inflammatory and antiviral mediators following infection with neurotropic DNA viruses. However, the mechanisms by which glia mediate such responses remain poorly understood. Recently, a class of intracellular pattern recognition receptors (PRRs), collectively known as DNA sensors, have been identified in both leukocytic and non-leukocytic cell types. The ability of such DNA sensors to initiate immune mediator production and contribute to infection resolution in the periphery is increasingly recognized, but our understanding of their role in the CNS remains limited at best. In this review, we describe the evidence for the expression and functionality of DNA sensors in resident brain cells, with a focus on their role in neurotropic virus infections. The available data indicate that glia and neurons can constitutively express, and/or can be induced to express, various disparate DNA sensing molecules previously described in peripheral cell types. Furthermore, multiple lines of investigation suggest that these sensors are functional in resident CNS cells and are required for innate immune responses to viral infections. However, it is less clear whether DNA sensormediated glial responses are beneficial or detrimental, and the answer to this question appears to dependent on the context of the infection with regard to the identity of the pathogen, host cell type, and host species. Defining such parameters will be essential if we are to successfully target these molecules to limit damaging inflammation while allowing beneficial host responses to improve patient outcomes.

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Targeting of the cGAS-STING system by DNA viruses

Cited by 29 publications

References 103 publications

African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

Circulating Mitochondrial DNA Stimulates Innate Immune Signaling Pathways to Mediate Acute Kidney Injury

Cytosolic DNA Sensors and CNS Responses to Viral Pathogens

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