Glutamine addiction in virus-infected mammalian cells: A target of the innate immune system?

Koufaris, Costas; Nicolaidou, Vicky

doi:10.1016/j.mehy.2021.110620

Cited by 5 publications

(12 citation statements)

References 41 publications

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“…Galactose was shown to anaplerotically feed TCA via L-glutamine production [29]. An open question in the literature is whether L-glutamine is essential for antiviral response or viral progeny [28]. In light of our previous results, we hypothesized that L-glutamine would be essential for the establishment of an effective antiviral response, via the supply of TCA and OXPHOS.…”

Section: Resultsmentioning

confidence: 99%

“…However, to date, the beneficial effect of glutamine during infection remained unclear. Indeed, it has been suggested that infected cells may be 'addicted' to glutamine, although it has not been established whether this addiction is due to the virus or rather to the requirement for glutamine to mount an effective antiviral response [28]. The work of Shiratori et al illustrates that the use of galactose to force the metabolic reprogramming of cancer cells toward OXPHOS relies on increasing the glutamine pool to anaplerotically generate TCA intermediates [29].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Dependency Shapes Bivalent Antiviral Response in Host Cells in response to poly:IC: The Role of Glutamine

Lebeau,

Paulo-Ramos,

Hoarau

et al. 2023

Preprint

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The establishment of effective antiviral responses within host cells is intricately related to their metabolic status, shedding light on immunometabolism. In this study, we investigated the hypothesis that cellular reliance on glutamine metabolism contributes to the development of a potent antiviral response. We evaluated the antiviral response in the presence or absence of L-glutamine in the culture medium, revealing a bivalent response hinging on cellular metabolism. While certain interferon-stimulated genes (ISGs) exhibited higher expression in an oxidative phosphorylation (OXPHOS)-dependent manner, others were surprisingly upregulated in a glycolytic-dependent manner. This metabolic dichotomy was influenced in part by variations in IFN-β expression. We initially demonstrated that the presence of L-glutamine induced an enhancement of oxidative phosphorylation in A549 cells. Furthermore, in cells stimulated poly:IC, a marked increase in ISGs expression was observed in a dose-dependent manner with L-glutamine supplementation. Interestingly, our findings unveiled a metabolic dependency in the expression of specific ISGs. In particular, genes such as ISG54, ISG12 and ISG15 exhibited heightened expression in cells cultured with L-glutamine, corresponding to higher OXPHOS rates and IFN-β signaling. Conversely, the expression of viperin and 2'-5'-oligoadenylate synthetase 1 was inversely related to L-glutamine concentration, suggesting a glycolysis-dependent regulation, confirmed by inhibition experiments. This study highlights the intricate interplay between cellular metabolism, especially glutaminergic and glycolytic, and the establishment of the canonical antiviral response characterized by the expression of antiviral effectors, potentially paving the way for novel strategies to modulate antiviral responses through metabolic interventions.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Dependency Shapes Bivalent Antiviral Response in Host Cells in response to poly:IC: The Role of Glutamine

Lebeau,

Paulo-Ramos,

Hoarau

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The degradation of the glucuronate pathway leads to proteoglycans production in the cell. 19 Considering influenza is an enveloped virus, activation of this pathway can be attributed to the influenza virus. Also, proteoglycans are required for proliferating and signal transduction during immune cell activity.…”

Section: Resultsmentioning

confidence: 99%

“…Activation of this pathway in our study indirectly indicates glycolysis in immune cells. The degradation of the glucuronate pathway leads to proteoglycans production in the cell 19 . Considering influenza is an enveloped virus, activation of this pathway can be attributed to the influenza virus.…”

Section: Discussionmentioning

confidence: 99%

The effect of influenza virus on the metabolism of peripheral blood mononuclear cells with a metabolomics approach

Karimi

Oskouie

Rezaie

et al. 2022

Journal of Medical Virology

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Respiratory viruses have led to many deaths and hospitalizations per year in the world. The influenza virus is one of the most important respiratory viruses. Recently, metabolic studies in viral infections have been widely studied by scientists.Metabolomics states the metabolites present in a living organism under certain conditions. In this study, peripheral blood mononuclear cells were spinoculated using a virus produced by the Madin-Darby canine kidney cell culture system, and cells were harvested following spinoculation by the influenza virus. Isolation of peripheral blood mononuclear cells was performed by Ficoll-Paque density gradient centrifugation.Metabolites were extracted using organic and water approaches. Metabolic profiling was performed by a nontargeted technique using liquid chromatography with tandem mass spectrometry. Multivariate analysis methods were used to determine the main variables. the metabolic pathways involved were determined using databases. Results of the present study showed changes in biosynthesis pathways such as lipids, polyamines, catecholamines, and vitamins. Findings also showed that it is possible to

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“…Among all nutrients, amino acids are traditionally considered to compose proteins, and recently have been reported to function as direct signals to activate several signaling pathways and further play multiple functions [ 28 ]. Glutamine (Gln) is an abundant amino acid in blood which also functions as the most important fuel for intestinal tissue to support gut protein synthesis [ 29 , 30 ], regulate antioxidant [ 31 ] and immune system [ 32 , 33 ], promote cell proliferation [ 34 ], and delay apoptosis [ 35 , 36 ]. Glutamine has also been reported to activate several cell signaling-related kinases to play multiple functions [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary Glutamine Inclusion Regulates Immune and Antioxidant System, as Well as Programmed Cell Death in Fish to Protect against Flavobacterium columnare Infection

et al. 2021

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The susceptibility of animals to pathogenic infection is significantly affected by nutritional status. The present study took yellow catfish (Pelteobagrus fulvidraco) as a model to test the hypothesis that the protective roles of glutamine during bacterial infection are largely related to its regulation on the immune and antioxidant system, apoptosis and autophagy. Dietary glutamine supplementation significantly improved fish growth performance and feed utilization. After a challenge with Flavobacterium columnare, glutamine supplementation promoted il-8 and il-1β expression via NF-κB signaling in the head kidney and spleen, but inhibited the over-inflammation in the gut and gills. Additionally, dietary glutamine inclusion also enhanced the systematic antioxidant capacity. Histological analysis showed the protective role of glutamine in gill structures. Further study indicated that glutamine alleviated apoptosis during bacterial infection, along with the reduced protein levels of caspase-3 and the reduced expression of apoptosis-related genes. Moreover, glutamine also showed an inhibitory role in autophagy which was due to the increased activation of the mTOR signaling pathway. Thus, our study for the first time illustrated the regulatory roles of glutamine in the fish immune and antioxidant system, and reported its inhibitory effects on fish apoptosis and autophagy during bacterial infection.

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Glutamine addiction in virus-infected mammalian cells: A target of the innate immune system?

Cited by 5 publications

References 41 publications

Metabolic Dependency Shapes Bivalent Antiviral Response in Host Cells in response to poly:IC: The Role of Glutamine

Metabolic Dependency Shapes Bivalent Antiviral Response in Host Cells in response to poly:IC: The Role of Glutamine

The effect of influenza virus on the metabolism of peripheral blood mononuclear cells with a metabolomics approach

Dietary Glutamine Inclusion Regulates Immune and Antioxidant System, as Well as Programmed Cell Death in Fish to Protect against Flavobacterium columnare Infection

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