Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I

PLoS Pathogens, Год журнала: 2023, Номер 19(5), С. e1011371 - e1011371

Опубликована: Май 1, 2023

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, impact of virus on glucose cells and subsequent effects are still unknown. Here, glycolysis induced by shown to facilitate replication promoting lactate production, which then attenuates interaction between mitochondrial antiviral-signaling protein (MAVS) retinoic acid-inducible gene I (RIG-I). induces PK-15 cells, as indicated significantly increased expression hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), superoxide dismutase-2 (SOD2) a dose-and replication-dependent manner, enhanced while reducing ATP generation. Overexpression PKM, PGK1, HIF-1α, PDK3 high concentrations promote replication, glycolytic inhibitors decrease it. Inhibition RLR signaling allowed better production attenuate MAVS RIG-I, regulatory effect was mainly via RIG-I signaling. infection mice PKM PGK1 tissues serum yields lactate. Mice treated with administered sodium showed elevated levels well suppressed induction interferon beta (IFNβ), IFNα, interferon-stimulated 15 (ISG15), interleukin 6 (IL-6). The inhibitory interferons lower oxamate low compared glucose, indicating that inhibited through vitro vivo . These results provide new perspective relationship innate immunity infection, suggesting or may be targets against virus.

Язык: Английский

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The Impact of Glycolysis and Its Inhibitors on the Immune Response to Inflammation and Autoimmunity

Molecules, Год журнала: 2024, Номер 29(6), С. 1298 - 1298

Опубликована: Март 14, 2024

Glucose metabolism is a crucial biological pathway maintaining the activation of extra- and intracellular signaling pathways involved in immune response. Immune cell stimulation via various environmental factors results their metabolic reprogramming to aerobic glycolysis. Different cells exhibit cell-type-specific patterns when performing functions. Numerous published studies have shed more light on importance system. Moreover, this knowledge for revealing new ways target inflammatory pathologic states, such as autoimmunity hyperinflammation. Here, we discuss role glycolysis activity physiological pathological conditions, potential use inhibitors disease treatment.

Язык: Английский

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Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012872 - e1012872

Опубликована: Янв. 13, 2025

Mitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival proliferation. Here, we report that infection with swine arterivirus porcine reproductive respiratory syndrome virus (PRRSV), manipulates mitochondria calcium ions (Ca2+) induce mitophagy, thereby reprogramming metabolism facilitate its own replication. Mechanistically, PRRSV-induced is caused by elevated levels Ca2+, derived from endoplasmic reticulum (ER) inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial uniporter (MCU) channels. This process associated increased mitochondria-associated membranes (MAMs), mediated upregulated expression sigma non-opioid intracellular (SIGMAR1). Elevated Ca2+ further activates Ca2+/CaM-dependent protein kinase β (CaMKKβ)-AMP-activated (AMPK)-dynamin-related (DRP1) signaling pathway, which interacts (FIS1) dynamics proteins 49 kDa (MiD49) promote fission. PRRSV infection, alongside fission, triggers mitophagy via PTEN-induced putative (PINK1)-Parkin RBR E3 ubiquitin (Parkin) promoting glycolysis excessive lactate production study reveals mechanism regulates during providing new insights into interplay between host cell metabolism.

Язык: Английский

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Reprogramming of glucose metabolism in virus infected cells

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 478(11), С. 2409 - 2418

Опубликована: Янв. 28, 2023

Язык: Английский

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Cellular metabolism hijacked by viruses for immunoevasion: potential antiviral targets

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 25, 2023

Cellular metabolism plays a central role in the regulation of both innate and adaptive immunity. Immune cells utilize metabolic pathways to modulate cellular differentiation or death. The intricate interplay between immune response is critical for maintaining homeostasis effective antiviral activities. In recent years, immunometabolism induced by viral infections has been extensively investigated, accumulating evidence indicated that can be hijacked facilitate replication. Generally, virus-induced changes lead reprogramming metabolites enzymes different (glucose, lipid, amino acid metabolism). Metabolic affects function cells, regulates expression molecules determines cell fate. Therefore, it important explore effector with immunomodulatory properties, including metabolites, enzymes, other immunometabolism-related as antivirals. This review summarizes relevant advances field infections, providing novel insights development

Язык: Английский

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PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 8, 2024

Abstract Host survival depends on the elimination of virus and mitigation tissue damage. Herein, we report modulation D-mannose flux rewires virus-triggered immunometabolic response cascade reduces Safe inexpensive can compete with glucose for same transporter hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species succinate-mediated hypoxia-inducible factor-1α, thus virus-induced proinflammatory cytokine production. The combinatorial treatment by antiviral monotherapy exhibits in vivo synergy despite delayed mouse model infections. Phosphomannose isomerase ( PMI ) knockout cells are viable, whereas addition to blocks cell proliferation, indicating that activity determines beneficial effect D-mannose. inhibition a panel replication via affecting host viral surface protein glycosylation. However, does not or fitness. Taken together, PMI-centered therapeutic strategy clears infection while reprograms glycolysis control collateral

Язык: Английский

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Lactate-lactylation-HSPA6 axis promotes PRRSV replication by impairing IFN-β production

Journal of Virology, Год журнала: 2023, Номер 98(1)

Опубликована: Дек. 13, 2023

Lactate, traditionally considered a metabolic by-product, has recently been identified as substrate for the induction of lactylation, newly epigenetic modification that plays an important role in regulation host gene expression. Our previous study showed lactate levels were significantly elevated cells infected with porcine reproductive and respiratory syndrome virus (PRRSV),

Язык: Английский

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Human Airway Basal Cells Undergo Reversible Squamous Differentiation and Reshape Innate Immunity

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2023, Номер 68(6), С. 664 - 678

Опубликована: Фев. 8, 2023

Histological and lineage immunofluorescence examination revealed that healthy conducting airways of humans animals harbor sporadic poorly differentiated epithelial patches mostly in the dorsal noncartilage regions remarkably manifest squamous differentiation.

Язык: Английский

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Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Авг. 5, 2024

Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in intestine and glycolysis lung tissues. In clinical guidelines for pneumonia treatment China, Ma Xing Shi Gan Decoction (MXSG) a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism action related to intestinal structure tissue glycolysis.

Язык: Английский

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White Spot Syndrome Virus Triggers a Glycolytic Pathway in Shrimp Immune Cells (Hemocytes) to Benefit Its Replication

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 4, 2022

White spot syndrome virus (WSSV) is the causative agent of a shrimp disease that inflicts in huge economic losses shrimp-farming industry. WSSV triggers aerobic glycolysis immune cells (hemocytes), but how this regulates glycolytic enzymes or pathway yet to be characterized. Therefore, mRNA levels and activity four important enzymes, Hexokinase (HK), Phosphofructokinase (PFK), Pyruvate kinase (PK), Lactate dehydrogenase (LDH), were measured WSSV-infected hemocytes. Gene expression HK PFK, not LDH PK, was increased at viral genome replication stage (12 hpi); furthermore, these except HK, concurrently increased. However, there no enzyme late (24 hpi). In vivo dsRNA silencing disruption by 2-DG further confirmed role replication. Based on tracing studies using stable isotope labeled glucose, activated stage, stage. This study demonstrated enhanced activating providing energy biomolecules for

Язык: Английский

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