Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus

mBio, Год журнала: 2023, Номер 14(5)

Опубликована: Окт. 5, 2023

Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, depends on host cells to provide energy needed produce progeny virions. Glycolysis a series oxidative reactions used metabolize glucose and cells. Therefore, glycolysis may be helpful infection. In this study, we show that increases by inducing stabilization, transcription, translation, activation hypoxia-inducible factor (HIF)-1α in infected cells, which important production This study contributes understanding molecular mechanism HIF-1α-mediated controls infection reveals an effective target development highly efficient anti-RSV drugs.

Язык: Английский

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Research progress of hexokinase 2 in inflammatory-related diseases and its inhibitors

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 264, С. 115986 - 115986

Опубликована: Ноя. 23, 2023

Язык: Английский

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Enteric coronavirus PDCoV evokes a non-Warburg effect by hijacking pyruvic acid as a metabolic hub

Redox Biology, Год журнала: 2024, Номер 71, С. 103112 - 103112

Опубликована: Март 4, 2024

The Warburg effect, also referred as aerobic glycolysis, is a common metabolic program during viral infection. Through targeted metabolomics combined with biochemical experiments and various cell models, we investigated the central carbon metabolism (CCM) profiles of cells infected porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus zoonotic potential. We found that PDCoV infection required glycolysis but decreased glycolytic flux, exhibiting non-Warburg effect characterized by pyruvic acid accumulation. Mechanistically, enhanced pyruvate kinase activity to promote anabolism, process generates concomitant ATP production. hijacked catabolism increase biosynthesis non-essential amino acids (NEAAs), suggesting essential hub for scavenge host energy metabolites. Furthermore, facilitated glutaminolysis synthesis NEAA pyrimidines optimal proliferation. Our work supports novel CCM model after provides potential anti-PDCoV drug targets.

Язык: Английский

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Decoding macrophage immunometabolism in human viral infection

Advances in protein chemistry and structural biology, Год журнала: 2024, Номер unknown, С. 493 - 523

Опубликована: Янв. 1, 2024

Язык: Английский

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Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

Free Radical Biology and Medicine, Год журнала: 2024, Номер 225, С. 910 - 924

Опубликована: Ноя. 1, 2024

Язык: Английский

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Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections

Open Biology, Год журнала: 2025, Номер 15(2)

Опубликована: Фев. 1, 2025

Glycolysis, present in most organisms, is evolutionarily one of the oldest metabolic pathways. It has great relevance at a physiological level because it responsible for generating ATP cell through conversion glucose into pyruvate and reducing nicotinamide adenine dinucleotide (NADH) (that may be fed electron chain mitochondria to produce additional by oxidative phosphorylation), as well producing intermediates that can serve substrates other processes. Glycolysis takes place 10 consecutive chemical reactions, each which catalysed specific enzyme. Although energy transduction metabolism main function this pathway, involvement virulence, growth, pathogen–host interactions, immunomodulation adaptation environmental conditions are functions attributed pathway. In humans, where glycolysis occurs mainly cytosol, mislocalization some glycolytic enzymes various subcellular locations, alterations their expression regulation, been associated with development progression diseases. review, we describe role pathogenesis diseases clinical interest. addition, potential these targets drug use diagnostic prognostic markers pathologies also discussed.

Язык: Английский

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Role of Hypoxia-Inducible Factors in Respiratory Syncytial Virus Infection-Associated Lung Disease

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3182 - 3182

Опубликована: Март 29, 2025

Hypoxia-inducible factors (HIFs) are transcription that enable cells to adapt low-oxygen environments. Viruses can exploit this pathway enhance infection, making HIF modulation a potential antiviral strategy. In previous in vitro studies, we found respiratory syncytial virus (RSV) stabilizes HIFs under normoxic conditions with inhibition of HIF-1α reducing replication. Despite several HIF-modulating compounds being tested or approved other non-infectious models, little is known about their efficacy against viruses relevant animal models. This study aimed characterize the disease-modulating properties and (PX478) HIF-2α PT2385 inhibitors RSV-infected BALB/c mice. We worsened clinical disease parameters while simultaneously improving airway function. Blocking also significantly reduced peak RSV replication lung. contrast, was associated improved parameters, no changes function, viral following infection. The analysis lung significant modification T-cell compartment correlated pathology titers for each inhibitor. underscores differential roles proteins infection highlights need further characterization currently use therapeutic consideration.

Язык: Английский

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Neospora caninum hijacks host PFKFB3-driven glycolysis to facilitate intracellular propagation of parasites

Veterinary Research, Год журнала: 2025, Номер 56(1)

Опубликована: Апрель 30, 2025

Язык: Английский

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PKM2 Facilitates Classical Swine Fever Virus Replication by Enhancing NS5B Polymerase Function

Viruses, Год журнала: 2025, Номер 17(5), С. 648 - 648

Опубликована: Апрель 29, 2025

Host metabolic reprogramming is a critical strategy employed by many viruses to support their replication, and the key enzyme plays important roles in virus infection. This study investigates role of pyruvate kinase M2 (PKM2), glycolytic with non-canonical functions, replication classical swine fever (CSFV). Using PK-15 cells piglet models, we demonstrate that CSFV infection upregulates PKM2 expression both vitro vivo, creating proviral environment. knockdown siRNA reduced proliferation, while overexpression significantly increased propagation, which was evaluated viral protein synthesis, genome progeny virion production. A direct interaction between NS5B identified co-immunoprecipitation GST-pulldown assays, affected polymerase activity dual-luciferase reporter assay, depletion reducing RdRp function 50%. Temporal analysis first cycle confirmed PKM2-dependent enhancement RNA synthesis. These findings establish as host factor directly binds potentiate activity, thereby bridging adaptation replication. provides new evidence physically interacting enhancing function, offering information about CSFV–host interaction.

Язык: Английский

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Metabolic reprogramming in viral infections: the interplay of glucose metabolism and immune responses

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 16, 2025

Metabolic reprogramming is an important player within the immune response to viral infections, allowing cells fine-tune their energy production and biosynthetic requirements while it actively working restrict pathogen access essential nutrients. Particularly, glucose metabolism, which appears be one of regulators function, affects cell activation, cytokine secretion, restriction. This review explores mechanisms metabolic during with a specific emphasis on metabolism. We discussed key cytokines involved in orchestrating this process influence pre-existing disorders efficiency. Furthermore, we introduced emerging therapeutic strategies that target metabolism enhance antiviral immunity improve disease outcomes. A deeper understanding interaction between could promising for development novel immunometabolic targets against infections.

Язык: Английский

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