SARS-CoV-2 Nsp2 Contributes to Inflammation by Activating NF-κB

Lacasse, Émile; Gudimard, Leslie; Dubuc, Isabelle; Gravel, Annie; Allaeys, Isabelle; Boilard, Éric; Flamand, Louis

doi:10.3390/v15020334

Cited by 14 publications

(5 citation statements)

References 54 publications

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“…The S protein activates the canonical pathway controlling the NLRP3 inflammasome in both mononuclear cells and neutrophils in patients [ 7 ]. The non-structural protein (NSP)2 triggers the transcription of NLRP3 protein through NF-κB signaling [ 8 ]. The N protein of SARS-CoV-2 directly binds to NLRP3 and triggers the formation of the NLRP3 inflammasome, thereby inducing excessive inflammatory response, acute lung injury, and accelerated sepsis-induced death [ 9 ].…”

Section: Nlrp3 Inflammasome and Sars-cov-2mentioning

confidence: 99%

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

Deng,

Li,

Zhang

et al. 2023

Viruses

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Inflammasome activation is exclusively involved in sensing activation of innate immunity and inflammatory response during viral infection. Accumulating evidence suggests that the manipulation of inflammasome assembly or its interaction with viral proteins are critical factors in viral pathogenesis. Results from pilot clinical trials show encouraging results of NLRP3 inflammasome suppression in reducing mortality and morbidity in SARS-CoV-2-infected patients. In this article, we summarize the up-to-date understanding of inflammasomes, including NLRP3, AIM2, NLRP1, NLRP6, and NLRC4 in various viral infections, with particular focus on RNA viruses such as SARS-CoV-2, HIV, IAV, and Zika virus and DNA viruses such as herpes simplex virus 1. We also discuss the current achievement of the mechanisms involved in viral infection-induced inflammatory response, host defense, and possible therapeutic solutions.

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Section: Nlrp3 Inflammasome and Sars-cov-2mentioning

confidence: 99%

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

Deng,

Li,

Zhang

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Plenty of cytokines and inflammatory indicators, like TNF-α, CRP, IL-1, and IL-6, have been related to the development of CKD ( 40 ). These inflammatory factors are closely linked to the triggering of the nuclear factor-κB (NF-κB) cascade ( 41 ). Such a pathway would induce mitochondrial dysfunction and increased amounts of reactive oxygen species (ROS) ( 42 , 43 ), and NF-κB may cause an inflammatory cytokine feedback loop that might maintain kidney inflammation ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Association between dietary inflammatory index and chronic kidney disease in middle-aged and elderly populations

Guo,

Lei,

Liu

et al. 2024

Front. Nutr.

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BackgroundA link between food-induced inflammation and common chronic diseases has been identified in studies. However, there was uncertainty about the influence of dietary inflammatory potential on the risk of chronic kidney disease (CKD) among middle-aged and older groups. Our research aimed to examine the connection between dietary inflammatory index (DII) to CKD in people aged 40 years and older.MethodsThis study comprised ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Linear associations of DII with CKD, low-eGFR, and albuminuria were examined using multiple logistic regression, whereas non-linear associations were assessed by smoothed curve fitting. Besides, we conducted subgroup analyses and interaction tests.ResultsOf the 23,175 middle-aged and older individuals, a total of 5,847 suffered from CKD, making up 25.23% of all participants. After adjustment for all covariates, we found that increased DII scores were positive with an increased hazard of CKD (OR = 1.08, 95% CI: 1.05, 1.10, p < 0.0001), and the same was shown between DII and low-eGFR (OR = 1.16, 95% CI: 1.13, 1.19, p < 0.0001). After further converting DII into categorical variables, the above relationship still existed. These relations were consistent in different ages, genders, BMI, whether smoking, whether suffering from hypertension, and whether suffering from diabetes, with no significant stratification differences (all P for interaction >0.05). Surprisingly, we did not find a statistically significant correlation of DII to albuminuria after complete adjustment for covariates (OR = 1.02, 95% CI: 1.00, 1.05, p = 0.0742). Even when DII was considered as a categorical variable, this relation was still not statistically significant. Furthermore, we found an association in the shape of a U between DII and low-eGFR in the fully adjusted model, with a turning point at a DII of 1.6.ConclusionOur findings indicated that middle-aged and older persons with greater levels of DII had a significantly higher risk of CKD.

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“…Both SARS-CoV and SARS-CoV-2 NSP1 proteins can inhibit IFN response. However, Lacasse et al (65) discovered that NSP2 of SARS-CoV-2 can activate the NF-κB pathway and the IFNβ promoter. They also found that NSP2 of SARS-CoV-2 partially counteracts the IFN inhibitory activity of NSP1.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication

Liu,

Lu,

et al. 2023

Front. Med.

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IntroductionSince its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses.MethodsIn this article, we comparatively analyzed publicly available transcriptome data of human cell lines infected with highly pathogenic SARS-CoV-2, SARS-CoV, MERS-CoV, and lowly pathogenic HCoV-229E. The host gene expression profiles during human coronavirus (HCoV) infections were generated, and the pathways and biological functions involved in immune responses, antiviral efficacy, and organ damage were intensively elucidated.ResultsOur results indicated that SARS-CoV-2 induced a stronger immune response versus the other two highly pathogenic HCoVs. Specifically, SARS-CoV-2 induced robust type I and type III IFN responses, marked by higher upregulation of type I and type III IFNs, as well as numerous interferon-stimulated genes (ISGs). Further Ingenuity Pathway Analysis (IPA) revealed the important role of ISGs for impeding SARS-CoV-2 infection, and the interferon/ISGs could be potential targets for therapeutic interventions. Moreover, our results uncovered that SARS-CoV-2 infection was linked to an enhanced risk of multi-organ toxicity in contrast to the other two highly pathogenic HCoVs.DiscussionThese findings provided valuable insights into the pathogenic mechanism of SARS-CoV-2, which showed a similar pathological feature but a lower fatality rate compared to SARS-CoV and MERS-CoV.

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SARS-CoV-2 Nsp2 Contributes to Inflammation by Activating NF-κB

Cited by 14 publications

References 54 publications

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

Association between dietary inflammatory index and chronic kidney disease in middle-aged and elderly populations

Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication

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