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Title:
Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans | GeroScience
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Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.
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Keywords {🔍}
rnai, pubmed, article, viral, google, scholar, infection, daf, antiviral, elegans, virus, survival, expression, day, adulthood, cas, reduced, immunity, reproduction, immune, rna, gene, central, riis, signalling, load, drh, model, iis, fig, treatment, data, cde, infected, individuals, pathways, age, caenorhabditis, orv, orsay, pathway, mortality, agespecific, longevity, absence, experimental, lifespan, ageing, increased, worms,
Topics {✒️}
n-ras-pi3k-akt-mtor pathway signaling-abortive anti-sars-cov-2 defense incomplete mark–recapture/recovery data single-stranded viral rna open access license disentangling life-history trade-offs cost-free anti-viral immunity anti-viral defence systems stress-related pathway components article download pdf boost anti-viral defence immunologie de marseille-luminy fed late-l4 larvae horizontal faecal-oral transmission[25 zoe de pasquale-crighton anti-viral rna interference circumvent parasite-induced reduction terminal uridylation-based degradation double-stranded rna anti-viral immune pathway nutrient-sensing iis pathway insulin/igf-1 signalling rna-based antiviral immunity normalised anti-viral gene anti-viral defence mechanisms rna helicase rig female-biased sex ratio improve anti-bacterial resistance improve anti-viral resistance anti-viral gene expression improve anti-viral immunity anti-viral immune pathways anti-viral immune response kullback–leibler divergence calibration time-staggered independent blocks anti-viral immunity pathways anti-viral transcriptional response qrt-pcr cycle thresholds increased anti-viral resistance rnai-based innate immunity caenorhabditis elegans rig shapiro–wilk normality test cellular integrity life history trade-offs anti-viral immune upregulation anti-viral rnai pathways naturally occurring polymorphism late-l4 orv-infected represents age-independent mortality innate immune system
Questions {❓}
- Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes?
- Immunosenescence and its hallmarks: how to oppose aging strategically?
- Trade-offs in evolutionary immunology: just what is the cost of immunity?
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headline:Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans
description:Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.
datePublished:2024-04-08T00:00:00Z
dateModified:2024-04-08T00:00:00Z
pageStart:5767
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Anti-viral immunity
Healthy aging
Orsay RNA virus
Rate-of-senescence
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Molecular Medicine
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headline:Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans
description:Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.
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Anti-viral immunity
Healthy aging
Orsay RNA virus
Rate-of-senescence
Cell Biology
Geriatrics/Gerontology
Molecular Medicine
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