Interferons: Reprogramming the Metabolic Network against Viral Infection

Raniga, Kavita; Liang, Chen

doi:10.3390/v10010036

Cited by 60 publications

(68 citation statements)

References 156 publications

(190 reference statements)

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“…MNV infection in RAW cells induces a strong innate immune response, including interferon induction (66). Type I Interferons in turn are able to affect host cell metabolism (67, 68), and exhibit a strong anti-MNV response (69–71). Therefore, we determined whether 2DG inhibition of viral replication was dependent on type I interferon responses.…”

Section: Resultsmentioning

confidence: 99%

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

Jia

Goodfellow

et al. 2018

Preprint

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word count: 227 13 Manuscript word count: 4830 14 15 16 ABSTRACT 17The metabolic pathways of central carbon metabolism, glycolysis and oxidative phosphorylation 18 (OXPHOS), are important host factors that determine the outcome of viral infections and can 19 therefore be manipulated by some viruses to favor infection. However, mechanisms of metabolic 20 modulation and their effects on viral replication vary widely. Herein, we present the first 21 metabolomics profile of norovirus-infected cells, which revealed increases in glycolysis, 22 IMPORTANCE 38Viruses depend on the host cells they infect to provide the machinery and substrates for 39 replication. Host cells are highly dynamic systems that can alter their intracellular environment 40 and metabolic behavior, which may be helpful or inhibitory for an infecting virus. In this study, 41 we show that macrophages, a target cell of murine norovirus (MNV), increase central carbon 42 metabolism upon viral infection, which is important for early steps in MNV infection. Human 43 noroviruses (hNoV) are a major cause of gastroenteritis globally, causing enormous morbidity 44 and economic burden. Currently, no effective antivirals or vaccines exist for hNoV, mainly due 45 to the lack of high efficiency in vitro culture models for their study. Thus, insights gained from 46 the MNV model may reveal aspects of host cell metabolism that can be targeted for improving 47 hNoV cell culture systems and for developing effective antiviral therapies. 48 49

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Section: Resultsmentioning

confidence: 99%

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

Jia

Goodfellow

et al. 2018

Preprint

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“…With respect to immunometabolism, mitochondrial metabolism shows a remarkable sensitivity to chemokine and IFN signaling [95,102]. For example, ISG15 is an interferon-stimulated, ubiquitin-like protein which regulates mitochondrial homeostasis and targets various proteins involved in catabolic autophagy metabolism in the mitochondria (mitophagy) during infection [103,104].…”

Section: Discussionmentioning

confidence: 99%

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Declerck¹,

Pérez-Novo²,

Grielens³

et al. 2020

Preprint

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Background: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.Methods: A system biology approach involving genomewide transcriptome, epigenome and kinome activity profiles was applied to characterize the immunomodulatory effects of a standardized Echinacea purpurea extract Echinaforce® in THP1 monocytes.Results: Gene expression and DNA methylation analysis revealed activation of innate immunity related antiviral signaling networks, involving IFN, chemotaxis and immunometabolic pathways. 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 by JAK1 responsive gene expression and epigenetic regulation of HERVs in monocytes, which supports its prophylactic use against common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2.

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“…Upon infection, cellular signaling through the innate immune response stimulates the expression of hundreds of interferon-stimulated genes (ISGs) that restrict virus replication. Several of the ISGs are metabolic enzymes, including SAMHD1 and IDO1, which deplete nucleotides and tryptophan, respectively, to limit virus replication [53]. Given their importance in virus replication, polyamines are similarly depleted upon virus infection.…”

Section: Polyamines In Mammalian Viruses and The Response To Infectionmentioning

confidence: 99%

Diverse Functions of Polyamines in Virus Infection

Firpo

Mounce

2020

Biomolecules

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As obligate intracellular parasites, viruses rely on host cells for the building blocks of progeny viruses. Metabolites such as amino acids, nucleotides, and lipids are central to viral proteins, genomes, and envelopes, and the availability of these molecules can restrict or promote infection. Polyamines, comprised of putrescine, spermidine, and spermine in mammalian cells, are also critical for virus infection. Polyamines are small, positively charged molecules that function in transcription, translation, and cell cycling. Initial work on the function of polyamines in bacteriophage infection illuminated these molecules as critical to virus infection. In the decades since early virus-polyamine descriptions, work on diverse viruses continues to highlight a role for polyamines in viral processes, including genome packaging and viral enzymatic activity. On the host side, polyamines function in the response to virus infection. Thus, viruses and hosts compete for polyamines, which are a critical resource for both. Pharmacologically targeting polyamines, tipping the balance to favor the host and restrict virus replication, holds significant promise as a broad-spectrum antiviral strategy.

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Interferons: Reprogramming the Metabolic Network against Viral Infection

Cited by 60 publications

References 156 publications

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Diverse Functions of Polyamines in Virus Infection

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