SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway

@article{Xu2020SARSCoV2VT,
  title={SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway},
  author={Huanzhou Xu and Siddhi A. Chitre and Ibukun A. Akinyemi and Julia C. Loeb and John A. Lednicky and Michael T. McIntosh and Sumita Bhaduri-McIntosh},
  journal={bioRxiv},
  year={2020}
}
Cytokine storm resulting from a heightened inflammatory response is a prominent feature of severe COVID-19 disease. This inflammatory response results from assembly/activation of a cell-intrinsic defense platform known as the inflammasome. We report that the SARS-CoV-2 viroporin encoded by ORF3a activates the NLRP3 inflammasome, the most promiscuous of known inflammasomes. ORF3a triggers IL-1β expression via NFκB, thus priming the inflammasome while also activating it via ASC-dependent and… 
Inflammasomes and SARS-CoV-2 Infection
TLDR
Current understanding of the activation and possible functions of different inflammasome structures during SARS-CoV-2 infection is provided and that to response caused by influenza A virus is compared.
Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients
TLDR
Targeted therapeutics to suppress inflammasome activation may have a positive effect on the reduction of hyperinflammation-induced hypercoagulopathy and cardiovascular disorders occurring as COVID-19 complications.
Inflammasome activation at the crux of severe COVID-19
TLDR
Evidence that SARS-CoV-2 directly or indirectly activates inflammasomes, which are large multiprotein assemblies that are broadly responsive to pathogen-associated and stress-associated cellular insults, leading to secretion of the pleiotropic IL-1 family cytokines (IL-1β and IL-18), and pyroptosis, an inflammatory form of cell death is reviewed.
SARS-CoV-2 may trigger inflammasome and pyroptosis in the central nervous system: a mechanistic view of neurotropism
TLDR
The possible role of inflammasome and its consequence pyroptosis following coronavirus infections as potential mechanisms of neurotropism by SARS-CoV-2 are reviewed and discussed.
Probiotics Regulating Inflammation via NLRP3 Inflammasome Modulation: A Potential Therapeutic Approach for COVID-19
TLDR
Evidence from preclinical studies indicates that probiotics may block virus invasion and replication through their metabolites, bacteriocins, and their ability to block Angiotensin-Converting Enzyme 2 (ACE2), and by stimulating the immune response through NLRP3 inflammasome regulation.
Persistent oxidative stress and inflammasome activation in CD14highCD16- monocytes from COVID-19 patients
TLDR
Findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation as well as its long-term outcomes.
Persistent Oxidative Stress and Inflammasome Activation in CD14highCD16− Monocytes From COVID-19 Patients
The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative
Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules
TLDR
The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19.
ORF3a Protein of Severe Acute Respiratory Syndrome Coronavirus 2 Inhibits Interferon-Activated Janus Kinase/Signal Transducer and Activator of Transcription Signaling via Elevating Suppressor of Cytokine Signaling 1
TLDR
It is demonstrated that ORF3a dampens IFN signaling via upregulating SOCS1, which suppressed STAT1 phosphorylation and accelerated JAK2 ubiquitin-proteasomal degradation, which contribute to the understanding of the mechanism of SARS-CoV-2 antagonizing host antiviral response.
Innate immunology in COVID-19—a living review. Part I: viral entry, sensing and evasion
TLDR
SARS-CoV-2 viral entry and the described immune evasion mechanisms are examined to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II.
...
1
2
3
...

References

SHOWING 1-10 OF 42 REFERENCES
Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome
TLDR
Direct evidence is provided that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages, highlighting the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP2 inflammaome activation.
Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux
TLDR
It is demonstrated that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation.
Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC
  • Kam-Leung Siu, Kit-San Yuen, D. Jin
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2019
TLDR
It is shown that the SARS‐CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor‐associated factor 3 (TRAF3)–mediated ubiquitination of apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC).
Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host
TLDR
Dampened activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in bat primary immune cells in response to infection with multiple zoonotic viruses is caused by decreased transcriptional priming, the presence of a unique splice variant and an altered leucine-rich repeat domain of bat NLRP3.
A promiscuous inflammasome sparks replication of a common tumor virus
TLDR
It is demonstrated that EBV dovetails its escape strategy to a key cellular danger-sensing mechanism, indicate that transcription may be regulated by KAP1 abundance aside from canonical regulation through its posttranslational modification, and mechanistically link diabetes, which frequently activates the NLRP3 inflammasome, to deregulation of a tumor virus.
Interferons and inflammasomes: Cooperation and counterregulation in disease.
Nlrp3 Inflammasome Activation in Type 2 Diabetes: Is It Clinically Relevant?
TLDR
Deactivation of the Nlrp3 inflammasome in obese type 2 diabetic patients that lose excess weight through lifestyle intervention is coupled with improved glucose homeostasis, suggesting that inflammaome may be a clinically relevant mechanism that links inflammation with type 2 diabetes.
Mechanisms of disease: inflammasome activation and the development of type 2 diabetes
TLDR
The new immunological mechanisms that link metabolic dysfunction to the emergence of chronic inflammation are outlined and the opportunities and challenges of future therapeutic approaches to dampen NLRP3 inflammasome activation or IL-1β signaling for controlling type 2 diabetes are discussed.
...
1
2
3
4
5
...