scholarly journals An alternative STAT signaling pathway acts in antiviral immunity in Caenorhabditis elegans

2017 ◽  
Author(s):  
Mélanie Tanguy ◽  
Louise Véron ◽  
Przemyslaw Stempor ◽  
Julie Ahringer ◽  
Peter Sarkies ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Antiviral Immunity ◽  
Antiviral Response ◽  
Evolutionary Trajectory ◽  
C Elegans ◽  
Regulatory Cascade ◽  
Innate Immune Signaling ◽  
Antiviral Innate Immunity ◽  
Reverse Genetic Screen

AbstractAcross metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode C. elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C. elegans STAT homologue STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 show increased resistance to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation we show that, in contrast to the mammalian pathway, STA-1 acts as a transcriptional repressor. Thus STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Using a reverse genetic screen we identify the SID-3 as a kinase upstream of STA-1 in the response to infection. Together, our work identifies a novel STAT regulatory cascade controlling its activity in antiviral resistance, illustrating the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms.

scholarly journals RAB1B interacts with TRAF3 to promote antiviral innate immunity

2019 ◽  
Author(s):  
Dia C. Beachboard ◽  
Moonhee Park ◽  
Madhuvanthi Vijayan ◽  
Dillon J. Fernando ◽  
Graham D. Williams ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Nucleic Acid ◽  
Adaptor Protein ◽  
Antiviral Response ◽  
Type I ◽  
Signaling Proteins ◽  
Over Expression ◽  
Signaling Complex ◽  
Innate Immune Signaling ◽  
Antiviral Innate Immunity

ABSTRACTNucleic acid-based antiviral innate immunity activates a signaling cascade that induces type I and type III interferons (IFNs), and other cytokines. This signaling, which is highly regulated, is initiated by pattern recognition receptors, such as RIG-I, that sense viral RNA and then signal to the adaptor protein, MAVS. This adaptor protein then recruits additional signaling proteins, including TRAF3 and TBK1, to form a signaling complex that results in IRF3 activation for transcriptional induction of IFN. Here, we show that the GTPase trafficking protein RAB1B positively regulates RIG-I signaling to promote IFN-β induction and the antiviral response. Over-expression of RAB1B increases RIG-I-mediated signaling to IFN-β, while deletion results in reduced signaling of this pathway. Additionally, this loss of RAB1B results in a dampened antiviral response, as Zika virus infection is enhanced in the absence of RAB1B. Importantly, we identified the mechanism of RAB1B action by determining that it interacts with TRAF3 to facilitate the interaction of TRAF3 with MAVS. Thus, we identified RAB1B as a regulator of TRAF3 to promote the formation of innate immune signaling complexes in response to nucleic acid sensing.

scholarly journals Perception of environmental polypeptides in C. elegans activates insulin/IGF signaling and alters lipid metabolism

2018 ◽  
Author(s):  
Rebecca E. W. Kaplan ◽  
Amy K. Webster ◽  
Rojin Chitrakar ◽  
Joseph A. Dent ◽  
L. Ryan Baugh
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Nile Red ◽  
Subsequent Development ◽  
Culture Conditions ◽  
C Elegans ◽  
Regulatory Cascade ◽  
Food Perception ◽  
Peptide Secretion ◽  
Igf Signaling

AbstractFood perception affects animal physiology in complex ways. We uncoupled the effects of food perception and ingestion in the roundworm C. elegans. Perception was not sufficient to promote development, but larvae exposed to food without ingestion failed to develop upon return to normal culture conditions. Inhibition of gene expression during perception rescued subsequent development, demonstrating the response to perception without feeding is deleterious. Perception altered DAF-16/FOXO localization, reflecting activation of insulin/IGF signaling (IIS). The insulin-like peptide daf-28 was specifically required, suggesting perception in chemosensory neurons directly regulates peptide secretion. Gene expression and Nile Red staining suggest that perception alters lipid metabolism. Environmental polypeptides are sensed by starved larvae and promote dauer diapause recovery. We conclude that polypeptides are perceived as a food-associated cue, initiating a signaling and gene regulatory cascade that alters metabolism in anticipation of feeding and development, but that this response is detrimental if feeding does not occur.

scholarly journals Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response

Hepatology ◽  
2011 ◽  
Vol 55 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Yasuhiro Asahina ◽  
Kaoru Tsuchiya ◽  
Masaru Muraoka ◽  
Keisuke Tanaka ◽  
Yuichiro Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Genetic Variation ◽  
Antiviral Response ◽  
Interleukin 28B

scholarly journals The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVS-mediated antiviral innate immunity

2019 ◽  
Vol 295 (2) ◽  
pp. 444-457 ◽  
Author(s):  
Kai Yasukawa ◽  
Daisuke Kinoshita ◽  
Keisuke Yaku ◽  
Takashi Nakagawa ◽  
Takumi Koshiba
Keyword(s):  
Innate Immunity ◽  
Sendai Virus ◽  
Function Analysis ◽  
Mitochondrial Dynamics ◽  
Antiviral Response ◽  
Mitochondrial Metabolism ◽  
Synthetic Analog ◽  
Type I ◽  
Metabolic Demand ◽  
Antiviral Innate Immunity

MicroRNAs (miRNAs) are small noncoding RNAs that suppress the expression of multiple genes and are involved in numerous biologic functions and disorders, including human diseases. Here, we report that two miRNAs, miR-302b and miR-372, target mitochondrial-mediated antiviral innate immunity by regulating mitochondrial dynamics and metabolic demand. Using human cell lines transfected with the synthetic analog of viral dsRNA, poly(I-C), or challenged with Sendai virus, we found that both miRNAs are up-regulated in the cells late after viral infection and ultimately terminate the production of type I interferons and inflammatory cytokines. We found that miR-302b and miR-372 are involved in dynamin-related protein 1 (DRP1)-dependent mitochondrial fragmentation and disrupt mitochondrial metabolism by attenuating solute carrier family 25 member 12 (SLC25A12), a member of the SLC25 family. Neutralizing the effects of the two miRNAs through specific inhibitors re-established the mitochondrial dynamics and the antiviral responses. We found that SLC25A12 contributes to regulating the antiviral response by inducing mitochondrial-related metabolite changes in the organelle. Structure–function analysis indicated that SLC25A12, as part of a prohibitin complex, associates with the mitochondrial antiviral-signaling protein in mitochondria, providing structural insight into the regulation of the mitochondrial-mediated antiviral response. Our results contribute to the understanding of how miRNAs modulate the innate immune response by altering mitochondrial dynamics and metabolic demand. Manipulating the activities of miR-302b and miR-372 may be a potential therapeutic approach to target RNA viruses.

scholarly journals Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ken Declerck ◽  
Claudina Perez Novo ◽  
Lisa Grielens ◽  
Guy Van Camp ◽  
Andreas Suter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pattern Recognition ◽  
Innate Immunity ◽  
Common Cold ◽  
Echinacea Purpurea ◽  
Janus Kinase ◽  
Dna Repeats ◽  
Dna Repeat ◽  
Tract Infections ◽  
Antiviral Innate Immunity

Abstract Background Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. Methods Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. Results Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. Conclusions Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.

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