bims-mevinf 2025-10-05 papers

Antioxid Redox Signal. 2025 Sep 30.

Epstein-Barr Virus Hijacks Redox Signaling via Glutathione Peroxidase 4 to Sustain Latency and Drive Gastric Cancer Progression.

Duo Shi, Yanhong Zhao, Xia Zhao, Zhiyuan Gong, Wen Liu, Ping Li, Yan Zhang, Bing Luo.

Aims: Epstein-Barr virus (EBV)-associated gastric cancer (GC) accounts for about 9% of GC patients, but its pathogenesis remains unclear. Glutathione peroxidase 4 (GPX4) is an important antioxidant enzyme that is highly expressed in various tumors and is associated with viral infections. This study aimed to clarify the relationship between EBV and GPX4 and the role of GPX4 in the occurrence and development of EBV-associated GC. Results: EBV infection leads to oxidative stress and excessive generation of reactive oxygen species (ROS) in GC cells. At the same time, EBV upregulates the expression of antioxidant enzyme GPX4 through the latent membrane protein 2A (LMP2A)/p62/Kelch-like ECH-associated protein 1(Keap1)/nuclear factor (erythroid-derived 2)-like 2 (NRF2) axis, eliminating excessive ROS to balance redox homeostasis and maintain its own survival. The high expression of GPX4 in GC inhibits EBV's immediate early lytic gene BZLF1 expression, thereby inhibiting EBV reactivation, and promotes cell migration and proliferation by upregulating lipocalin-2 (LCN2). Innovation: This study is the first to demonstrate that EBV-induced GPX4 expression via the LMP2A/p62/Keap1/NRF2 axis contributes to both viral latency and tumor progression in GC. Conclusion: EBV activates the p62/Keap1/NRF2 signaling pathway through LMP2A to upregulate the expression of GPX4, thereby alleviating oxidative stress caused by viral infection and maintaining the redox homeostasis in GC cells. Such enhanced expression not only maintains the latent infection of EBV but also promotes the malignant transformation of GC cells through LCN2. Antioxid. Redox Signal. 00, 000-000.

Keywords: EBV; GPX4; LMP2A; gastric cancer; redox

DOI: https://doi.org/10.1177/15230864251382885

bioRxiv. 2025 Sep 27. pii: 2025.09.25.676695. [Epub ahead of print]

Central carbon metabolism switching in lytic versus temperate coral reef viral communities.

Coral reefs are declining globally due in part to bacterial overgrowth, a process known as microbialization. However, the role of bacteriophages that may inhibit microbialization by infecting and killing these bacteria remains poorly understood, especially their metabolic impacts on bacterial proliferation. To address this, we analyzed central carbon metabolism gene frequencies in viral communities from healthy (lytic-dominated) and degraded (temperate-dominated) Central Pacific coral reefs. We found that viral metabolism shifted broadly from being dominated by metabolism that builds up pools of central intermediates on degraded reefs dominated by temperate viral infection ('anaplerotic' reactions) to metabolism that consumes these pools to prioritize production of metabolic precursors for virion construction on healthy reefs dominated by lytic infection ('cataplerotic' reactions). This switch was shown by the over-representation of Entner-Doudoroff (ED) glycolysis genes on degraded, temperate-dominated reefs and of pentose phosphate pathway (PPP) and reductive tricarboxylic acid cycle (TCA) genes on healthy, lytic-dominated reefs. As a result of this metabolic dichotomy, our qualitative compartment modeling revealed two distinct ecosystem states: (i) healthy reefs, where lytic viral metabolism enhances viral production and suppresses bacterial overgrowth, and (ii) degraded reefs, where temperate viral metabolism accelerates bacterial proliferation. Because viral switching between lytic and temperate lifestyles is a known function of host physiological state, these findings position viral metabolism as both a driver of reef decline and a conservation lever, with metabolically mediated 're-viralization' offering a novel strategy to restore reef resilience.
Significance: Coral reefs are collapsing worldwide due to "microbialization," where algae-fueled bacteria overgrow corals. Viruses that infect these bacteria can suppress this process through lysis, but on degraded reefs they often switch to nonlethal temperate lifestyles, accelerating decline. Here we show that similar shifts occur in virus-encoded metabolism. On healthy reefs, lytic viruses carry genes that drain host metabolites to fuel virus production, which likely enhances infection and lysis rates and limits bacterial overgrowth. On degraded reefs, temperate viruses encode reactions that expand host metabolite pools, supporting bacterial proliferation. Thus, viral metabolism can either reinforce reef resilience or exacerbate collapse, making it a hidden driver of ecosystem fate and a potential target for conservation strategies.

DOI: https://doi.org/10.1101/2025.09.25.676695

J Med Virol. 2025 Oct;97(10): e70625

RSV-Induced Glutaric Acid Modulates Neuronal Mitochondrial Heterogeneity via the Lung-Brain Axis.

Taorui Du, Ousman Bajinka, Amie N Joof, Yurong Tan, Ling Chu.

The study was designed to explore how glutaric acid induced by respiratory syncytial virus (RSV) infection affects nerve cell mitochondrial heteroplasmy. An RSV infection animal model was established, and lung tissues were collected after 7 days for metabolomic analysis. Then, a neuroinflammatory cell model was constructed with lipopolysaccharide (LPS). The CCK8 assay detected proliferation, the DCFH-DA probe assessed reactive oxygen species (ROS) levels, and ELISA measured IL-1, IL-4, IL-6, and IFN-γ levels in HT-22 cells. RT-qPCR detected Drp1 and Mfn2 expression levels to study the mechanism of glutaric acid-exacerbated neuroinflammation. Immunofluorescence and RT-qPCR detected the effects of glutaric acid on neuron biomarkers in the lung (PGP9.5) and brain (NeuN). Bioinformatics screened glutaric acid-interacting proteins, and the enzymatic activities of NAD-dependent malate dehydrogenase (NAD-ME) were validated at cellular and animal levels. High-performance liquid chromatography (HPLC) detected glutaric acid content in blood and brain tissues. After glutaric acid treatment, Drp1 protein expression increased, Mfn2 decreased, and ROS, IL-1, and IL-6 cytokine levels rose significantly. Glutaric acid affects the central nervous system by disrupting the lung neural network, causing mitochondrial homeostasis dysregulation. Its interaction with NAD-ME accelerates mitochondrial imbalance. Glutaric acid induced by RSV infection aggravates neuroinflammation by affecting nerve cell mitochondrial homeostasis via the lung-brain axis. These findings offer new insights into RSV-induced neuroinflammation and potential targets for neuroprotective strategies.

Keywords: glutaric acid; lung−brain axis; mitochondrial heterogeneity; respiratory syncytial virus

DOI: https://doi.org/10.1002/jmv.70625

Virol Sin. 2025 Sep 27. pii: S1995-820X(25)00134-8. [Epub ahead of print]

HBV and host metabolic crosstalk: reprogramming pathways for viral replication and pathogenesis.

YanYing Yan, Zhiqiang Wei, Min Zheng, Mengji Lu, Xueyu Wang.

Hepatitis B virus (HBV) establishes chronic infection through strategic manipulation of host metabolic networks, driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma. Mechanistically, HBV reprograms core metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipid homeostasis, to fuel its replication machinery and evade immune surveillance. This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring, with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.

Keywords: HBV; TCA cycle; glycolysis; lipid metabolism; metabolic rewiring; oxidative phosphorylation

DOI: https://doi.org/10.1016/j.virs.2025.09.008

Front Nutr. 2025 ;12 1608300

Micronutrient status and fatty acid profile of adults with SARS-CoV-2 infection-an observational study.

Melanie Bleffgen, Laura Schinhammer, Francesco Giuseppe De Rosa, Silvia Scabini, Beate Brandl, Hans Hauner, Simona Bo, Thomas Skurk.

Introduction: SARS-CoV-2 infection is a complex disease with multiple dimensions, involving factors that promote infection and virus-driven processes in many body organs. The micronutrient status, beyond others, acts as a potential confounder, influencing susceptibility to infection and disease severity. Additionally, the virus appears to alter lipid metabolism, which may serve a dual function, suppor viral replication while simultaneously contributing to the body's defense and repair mechanisms.
Methods: This observational study compared micronutrient levels (vitamin D, selenium, zinc, magnesium, and iron) and lipid profiles between 139 SARS-CoV-2 -positive patients (62 hospitalized, 77 home care) and 314 healthy controls, using dried blood spots. We also examined differences by treatment setting (hospitalized vs. home care) as a proxy for disease severity.
Results: Patients with SARS-CoV-2 infection exhibited similar micronutrient levels but showed a significantly impaired lipid profile compared to healthy controls. Notably, there was a significant decrease in palmitic (p-value < 0.01) and stearic acid levels (p-value < 0.01) and a significant increase in omega-3 and omega-6 PUFAs, like AA (p-value < 0.01), DHA (p-value < 0.01), and EPA (p-value < 0.05) were detected. In the SARS-CoV-2 positive cohort, hospitalized patients had significantly lower micronutrient levels (p < 0.01 for all measured micronutrients) compared to those receiving home care.
Discussion: These findings suggest that SARS-CoV-2 infection alters lipid metabolism and that lower micronutrient status may be linked to greater disease severity.

Keywords: COVID-19; SARS-CoV-2; dried blood spots; fatty acid profile; micronutrient status; observational study; polyunsaturated fatty acids (PUFAs); vitamin D

DOI: https://doi.org/10.3389/fnut.2025.1608300

J Virol. 2025 Oct 01. e0102525

Intracellular iron positively modulates the replicative cycle of mimiviruses, increasing virus production.

Juliana Dos Santos Oliveira, Claudia F Dick, Gabriel Henrique Pereira Nunes, Victor Alejandro Essus, Jason Schrad, Sundharraman Subramanian, Jônatas Abrahão, José Roberto Meyer-Fernandes, Kristin Parent, Juliana Reis Cortines.

Mimiviruses, members of the Nucleocytoviricota phylum, produce large, pseudo-icosahedral virions densely coated with fibrils, except at a specialized fivefold vertex known as the stargate. Stargate opening is essential for delivering the viral core into the cytoplasm of phagocytic amoebae. These professional phagocytes deploy antimicrobial mechanisms such as the modulation of transition metal concentrations within phagolysosomes to eliminate internalized pathogens. Yet, mimiviruses have evolved striking adaptations to resist such hostile environments and initiate replication within these compartments. Here, we investigated the role of metal ions-particularly iron-in the replication of three giant viruses: Acanthamoeba polyphaga mimivirus (APMV), Antarctica virus, and Tupanvirus (TPV). We show that infection by these viruses increases cellular iron uptake and that elevated intracellular iron enhances viral replication. These findings reveal a previously underappreciated facet of the mimivirus-host interaction, in which iron availability acts as a positive modulator of the viral replicative cycle.IMPORTANCEGiant viruses like Mimivirus infect amoebae, which normally destroy microbes using toxic conditions inside cellular compartments. This study shows that, instead of being harmed, these viruses benefit from one of those supposedly hostile factors: iron. Through this work, we discovered that infection by Mimivirus and related viruses increases the host cell's iron uptake-and that more iron boosts virus production by the host cell. This reveals a surprising twist in the virus-host relationship: what should be a defense mechanism is turned into an advantage by the virus. By highlighting iron as a key factor in viral success, this work opens new perspectives on how giant viruses adapt to-and even exploit-the internal environment of their hosts. It also adds an important piece to our understanding of the complex strategies viruses use to survive and thrive inside cells.

Keywords: Acanthamoeba polyphaga mimivirus; Tupanvirus; iron; nutritional immunity; stargate

DOI: https://doi.org/10.1128/jvi.01025-25