Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Shi, Fushan; Lv, Qian; Wang, Tingjun; Xu, Jie; Xu, Wei; Shi, Yi; Fu, Xinyu; Yang, Taowei; Yang, Yang; Zhuang, Lenan; Fang, Weihuan; Gu, Jinyan; Li, Xiaoliang

doi:10.1128/mbio.02739-21

Cited by 36 publications

(41 citation statements)

References 59 publications

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“…The Nsp5 protease cut human TAB1, the intracellular pattern recognition receptor NLRP12 (Moustaqil et al, 2021), and human gasdermin (Shi et al, 2022).…”

Section: Nsp5mentioning

confidence: 99%

Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern

Godbold

Hewitt

Kappell

et al. 2023

Front. Bioeng. Biotechnol.

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Regulation of research on microbes that cause disease in humans has historically been focused on taxonomic lists of ‘bad bugs’. However, given our increased knowledge of these pathogens through inexpensive genome sequencing, 5 decades of research in microbial pathogenesis, and the burgeoning capacity of synthetic biologists, the limitations of this approach are apparent. With heightened scientific and public attention focused on biosafety and biosecurity, and an ongoing review by US authorities of dual-use research oversight, this article proposes the incorporation of sequences of concern (SoCs) into the biorisk management regime governing genetic engineering of pathogens. SoCs enable pathogenesis in all microbes infecting hosts that are ‘of concern’ to human civilization. Here we review the functions of SoCs (FunSoCs) and discuss how they might bring clarity to potentially problematic research outcomes involving infectious agents. We believe that annotation of SoCs with FunSoCs has the potential to improve the likelihood that dual use research of concern is recognized by both scientists and regulators before it occurs.

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“…The Nsp5 protease cut human TAB1, the intracellular pattern recognition receptor NLRP12 (Moustaqil et al, 2021), and human gasdermin (Shi et al, 2022).…”

Section: Nsp5mentioning

confidence: 99%

Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern

Godbold

Hewitt

Kappell

et al. 2023

Front. Bioeng. Biotechnol.

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“…Overall, the mechanisms by which viruses inhibit pyroptosis remain largely unknown. However, plus sense RNA viruses, such as Coronaviridae, utilize viral proteases to inhibit pyroptosis [182][183][184] (Table 2). Highly conserved viral proteases, such as NSP5 in coronaviruses, directly bind and cleave Gasdermin D in porcine and human cells, producing a truncated N-terminal Gasdermin D, lacking essential residues from caspase-1 cleavage [98].…”

Section: Viral-mediated Inhibition Of Pyroptosismentioning

confidence: 99%

Viral-mediated activation and inhibition of programmed cell death

et al. 2022

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Viruses are ubiquitous intracellular genetic parasites that heavily rely on the infected cell to complete their replication life cycle. This dependency on the host machinery forces viruses to modulate a variety of cellular processes including cell survival and cell death. Viruses are known to activate and block almost all types of programmed cell death (PCD) known so far. Modulating PCD in infected hosts has a variety of direct and indirect effects on viral pathogenesis and antiviral immunity. The mechanisms leading to apoptosis following virus infection is widely studied, but several modalities of PCD, including necroptosis, pyroptosis, ferroptosis, and paraptosis, are relatively understudied. In this review, we cover the mechanisms by which viruses activate and inhibit PCDs and suggest perspectives on how these affect viral pathogenesis and immunity.

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“…More recently, researchers have reported that GZMA from cytotoxic lymphocytes cleaves GSDMB and GZMB from natural killer cells, and cytotoxic T lymphocytes cleave GSDME to trigger pyroptosis in tumor cells [ 37 , 75 ]. Moreover, neutrophil elastase, porcine epidemic diarrhea virus and Cathepsin G directly cleave GSDMD to induce pyroptosis [ 73 , 74 , 93 ]. SpeB also cleaves GSDMA and triggers pyroptosis [ 77 ].…”

Section: Molecular Mechanisms Of Pyroptosis In Ocular Diseasesmentioning

confidence: 99%

Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

Chen

Rong

Xia

2022

J Neuroinflammation

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Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents and pro-inflammatory mediators (cytokines), including IL‐1β and IL‐18. It differs from other types of programmed cell death such as apoptosis, autophagy, necroptosis, ferroptosis, and NETosis in terms of its morphology and mechanism. As a recently discovered form of cell death, pyroptosis has been demonstrated to be involved in the progression of multiple diseases. Recent studies have also suggested that pyroptosis is linked to various ocular diseases. In this review, we systematically summarized and discussed recent scientific discoveries of the involvement of pyroptosis in common ocular diseases, including diabetic retinopathy, age-related macular degeneration, AIDS-related human cytomegalovirus retinitis, glaucoma, dry eye disease, keratitis, uveitis, and cataract. We also organized new and emerging evidence suggesting that pyroptosis signaling pathways may be potential therapeutic targets in ocular diseases, hoping to provide a summary of overall intervention strategies and relevant multi-dimensional evaluations for various ocular diseases, as well as offer valuable ideas for further research and development from the perspective of pyroptosis.

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Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Abstract: Recently, GSDMD has been reported as a key executioner for pyroptosis. This study first demonstrates the molecular mechanism of pGSDMD-mediated pyroptosis and that the pGSDMD-mediated pyroptosis protects host cells against PEDV infection.

Cited by 36 publications

References 59 publications

Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern

Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern

Viral-mediated activation and inhibition of programmed cell death

Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

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