Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

Allen, Charles N. S.; Arjona, Sterling P.; Santerre, Maryline; Sawaya, Bassel E.

doi:10.3390/v14030602

Cited by 34 publications

(31 citation statements)

References 286 publications

(328 reference statements)

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“…Recently, it has been shown that metabolic reprogramming due to viruses’ infection can result in increased glycolysis and decreased TCA cycle and increases the production of advanced glycation end-products (AGEs) [ 46 ]. AGES can be formed spontaneously from increased glycolytic intermediates and oxidative stress [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…We also demonstrated that the viral proteins alter the glycolysis pathway resulting in increased glycolytic intermediates and decreased pyruvate. This phenomenon has a precedent where viruses use this pathway to replicate [ 46 ]. Studies showed that HCV deregulates the mitochondria, promotes HIF-1α, and activates the glycolysis pathway [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrated that HIV-1 gp120 protein causes comparative symptoms in neurons [ 44 ]. We also showed that metabolic reprogramming is composed of seven hallmarks, and any disruption of these hallmarks can lead to the accumulation of RAGEs and chronic inflammation; however, the role of RAGE remains understudied [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

Allen

Santerre

Arjona

et al. 2022

Viruses

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Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

Allen

Santerre

Arjona

et al. 2022

Viruses

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“…Thus, the climbing behaviour of infected larvae was increased by glucose supplementation, and inhibited by insulin treatment, DCA or 2-DG treatment, and dietary restriction, confirming that reduced metabolic activity impeded climbing behaviour. Inhibition of the TCA cycle with DCA had more dramatic effects on HearNPV loads and climbing behaviour compared with inhibition of glycolysis with 2-DG, probably reflecting the greater importance of the TCA cycle in supplying cellular energy (Allen et al, 2022), which is critical for insect locomotion (Hassan et al, 2021). The full set of treatments and observed responses is summarized schematically in Figure 8.…”

Section: Discussionmentioning

confidence: 99%

Metabolic reprogramming of Helicoverpa armigera larvae by HearNPV facilitates viral replication and host immune suppression

et al. 2022

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Baculoviruses are highly evolved parasites that genetically reprogram the developing phenotype of their host insect to produce a vessel for virus replication and dispersal.Here we show that larvae of Helicoverpa armigera infected with HearNPV accumulate glucose in the midgut, which reduces food consumption and alters the dynamics of pathways governing metabolism and immunity. We used transcriptomics to demonstrate the role of the insulin signalling pathway in regulating the HearNPV infection process. Dietary restriction decreased mortality of infected larvae and reduced viral replication prior to death, whereas dietary supplementation with glucose produced the opposite effects. The expression of most tricarboxylic acid cycle (TCA) and energy metabolism-related genes was reduced in infected larvae, whereas the expression of immunity-, glycolysis-and insulin-related genes was enhanced. Treatment of infected larvae with insulin increased their survival, reduced viral replication and inhibited climbing behaviour compared to a control treatment with DMSO, whereas RNAi suppression of the insulin receptor gene produced the opposite effects. Inhibition of glycolysis with dichloroacetate (DCA) promoted viral replication and accelerated larval death, but inhibition of the TCA cycle with 2-deoxyglucose (2-DG) did not, although both diminished climbing behaviour. This work demonstrates that successful baculovirus infections hinge on metabolic reprogramming of the host and concurrent suppression of immune responses in the larval midgut, with the insulin signalling pathway mediating a trade-off between glucose metabolism and virus resistance.

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“…Like cellular miRNAs, v-miRNAs can target and regulate viral gene expression (including cellular gene expression) to modulate the active and latent switch modes. Maintenance of the viral latent phase is key to viral immune evasion and v-miRNAs are active participants in this process (reviewed in [ 168 ]). For example, EBV BART miRNAs play a significant role in controlling the viral life cycle, and thus maintaining latency.…”

Section: Persistent Viral Infection and Oncogenesis: V-mirnas As Effe...mentioning

confidence: 99%

Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

et al. 2022

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About 15% of all human cancers have a viral etiology. Although progress has been made, understanding the viral oncogenesis and associated molecular mechanisms remain complex. The discovery of cellular miRNAs has led to major breakthroughs. Interestingly, viruses have also been discovered to encode their own miRNAs. These viral, small, non-coding miRNAs are also known as viral-miRNAs (v-miRNAs). Although the function of v-miRNAs largely remains to be elucidated, their role in tumorigenesis cannot be ignored. V-miRNAs have also been shown to exploit the cellular machinery to benefit viral replication and survival. Although the discovery of Hepatitis C virus (HCV), and its viral miRNAs, is a work in progress, the existence of HPV-, EBV-, HBV-, MCPyV- and KSHV-encoded miRNA has been documented. V-miRNAs have been shown to target host factors to advance tumorigenesis, evade and suppress the immune system, and deregulate both the cell cycle and the apoptotic machinery. Although the exact mechanisms of v-miRNAs-induced tumorigenesis are still unclear, v-miRNAs are active role-players in tumorigenesis, viral latency and cell transformation. Furthermore, v-miRNAs can function as posttranscriptional gene regulators of both viral and host genes. Thus, it has been proposed that v-miRNAs may serve as diagnostic biomarkers and therapeutic targets for cancers with a viral etiology. Although significant challenges exist in their clinical application, emerging reports demonstrate their potent role in precision medicine. This review will focus on the roles of HPV-, HCV-, EBV-, HBV-, MCPyV-, and KSHV-produced v-miRNAs in tumorigenesis, as effectors in immune evasion, as diagnostic biomarkers and as novel anti-cancer therapeutic targets. Finally, it will discuss the challenges and opportunities associated with v-miRNAs theranostics in precision oncology.

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Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

Cited by 34 publications

References 286 publications

SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

Metabolic reprogramming of Helicoverpa armigera larvae by HearNPV facilitates viral replication and host immune suppression

Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

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