scholarly journals Caspase-dependent cleavage of DDX21 suppresses host innate immunity

2021 ◽  
Author(s):  
Chan Ding ◽  
Yingjie Sun ◽  
Wei Wu ◽  
Yang Qu ◽  
Shengqing Yu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Ribosomal Rna ◽  
Potential Role ◽  
Rna Virus ◽  
Rna Helicases ◽  
Immune Balance ◽  
Ribosomal Rna Processing ◽  
Antiviral Innate Immunity

DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been proven to contribute to antiviral innate immunity. DDX21 RNA helicase was identified as a nuclear protein involved in ribosomal RNA processing and RNA unwinding. DDX21 was also proved to be the scaffold protein in the complex of DDX1-DDX21-DHX36 which senses double strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleave DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus.

Chicken miR-126-5p Negatively Regulates Antiviral Innate Immunity By Targeting TRAF3

2021 ◽  
Author(s):  
Jie Wang ◽  
Yuqiang Cheng ◽  
Longlong Wang ◽  
Zhenyu Lin ◽  
Wenxian Zhu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cell Model ◽  
Rna Virus ◽  
Luciferase Reporter ◽  
Endogenous Expression ◽  
Immune Balance ◽  
Candidate Target ◽  
Candidate Target Gene ◽  
Antiviral Innate Immunity

Abstract Background Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessively activated is detrimental to immune homeostasis and even leads to "cytokine storm" of the infected host. A series of negative regulatory mechanisms are developed by the host to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. Results In this study we found that the miR-126-5p is markedly up-regulated in RNA virus infected chickens in GEO database. Then, the upregulation of the miR-126-5p by RNA virus was further verified via both cell model and in vivo test. Overexpression of miR-126-5p significantly inhibits the expression of interferon related genes and inflammatory cytokines evoked by RNA virus. The opposite result was achieved after knocking down miR-126-5p expression. Bioinformatics analysis indicated TRAF3 as the candidate target gene of miR-126-5p, and experimental evidence, such as the effects of miR-126-5p on the endogenous expression of TRAF3, and the effect of miR-126-5p on TRAF3 3'UTR drove luciferase reporter assay, were provided to further verify that miR-126-5p targets TRAF3. Furthermore, we demonstrated that miR-126-5p negatively regulates innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with co-expression assay. Conclusion Our results suggest that miR-126-5p is involved in the negative regulation of the chicken innate immunity, which might contribute to maintaining immune balance.

scholarly journals Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity

mBio ◽  
2021 ◽  
Author(s):  
Wei Wu ◽  
Yang Qu ◽  
Shengqing Yu ◽  
Sa Wang ◽  
Yuncong Yin ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Rna Processing ◽  
Rna Helicases ◽  
Host Innate Immunity ◽  
Rna Unwinding ◽  
Antiviral Innate Immunity

Innate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu) box RNA helicases, originally considered to be involved in RNA processing and RNA unwinding, have been shown to play an important role in antiviral innate immunity.

scholarly journals Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses

2021 ◽  
Vol 17 (9) ◽  
pp. e1009901
Author(s):  
Min Zhao ◽  
Yaolin Zhang ◽  
Xiqin Yang ◽  
Jiayang Jin ◽  
Zhuo Shen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Nuclear Translocation ◽  
Rna Viruses ◽  
Rna Virus ◽  
Innate Immune ◽  
Type I ◽  
Gene Promoters ◽  
Post Translational Modification

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

scholarly journals NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

2010 ◽  
Vol 70 (4) ◽  
pp. 668-674 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Systemic Sclerosis ◽  
Potential Role ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Fibrosing Alveolitis ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

The Potential Role of Innate Immunity in the Pathogenesis of Hodgkin's Lymphoma

2007 ◽  
Vol 21 (5) ◽  
pp. 805-823 ◽  
Author(s):  
Gunilla Enblad ◽  
Daniel Molin ◽  
Ingrid Glimelius ◽  
Marie Fischer ◽  
Gunnar Nilsson
Keyword(s):  
Innate Immunity ◽  
Hodgkin’S Lymphoma ◽  
Potential Role ◽  
Hodgkin's Lymphoma

CORONAVIRUS: Pathology, Immunology and Therapies.

2020 ◽  
pp. 1-17
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Severe Acute Respiratory Syndrome ◽  
Effective Treatment ◽  
Common Cold ◽  
Rna Virus ◽  
Clinical Protocols ◽  
Biochemical Mechanism ◽  
The Family

Abstract Coronavirus is a family of positive single-stranded RNA virus belonging to the family of coronaviridae. Coronavirus-19 infection (COVID-19) has appeared in 2019 and so there is no effective treatment that can eradicate it. The objective of this review is to present data on cellular and molecular characteristic of virus infection and also elucidate all molecular associated events with covid-19 infection in patients. The infection in humans can cause diseases ranging from a common cold to more serious diseases such as severe acute respiratory syndrome (SARS). The disease that it transmits (Covid-19) cannot be cured with conventional treatments. However, a large number of protocols have been implemented based on the sequels that it produces. In this review we summarize 1) the role of immune system against this pathogen as well as the biochemical mechanism by which squealed is responsible for disease progression 2) the possibility or not that patients who have suffered the disease have antibodies against the virus and 3) the clinical protocols used in order to mitigate induced-damage by virus.

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