bims-mevinf 2025-08-03 papers

bims-mevinf

Biomed News

on Metabolism in viral infections

Issue of 2025–08–03
eight papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology

Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus.
An untargeted metabolomics analysis in feces and brain of Orthoflaviviruses-infected mice.
Multi-omics profiling reveals infectious bursal disease virus-induced alterations in gene expression and metabolism in chicken bursa of fabricius.
Significant Increase of Cinnamic Acid in Metabolites of Chicks Infected with Infectious Bronchitis Virus and Its Remarkable Antiviral Effects In Vitro and In Vivo.
Lactylation and viral infections: A novel link between metabolic reprogramming and immune regulation.
Metabolomic evidence of bovine leukemia virus regulation on ferroptosis in bovine mammary epithelial cells.
HBx Drives Liver Cancer Stem Cell Generation Through Stimulating Glucose Metabolic Reprogramming.
ER Stress Disrupts the Airway Epithelium and Reduces Host Defense during Influenza A Virus Infection.

Biomolecules. 2025 Jul 16. pii: 1027. [Epub ahead of print]15(7):

Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus.

Jordi Camps, Simona Iftimie, Andrea Jiménez-Franco, Antoni Castro, Jorge Joven.

  Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to support replication, modulate immune responses, and promote disease progression. Emerging evidence shows that they induce metabolic reprogramming, shifting cellular energy production toward glycolysis to meet the bioenergetic demands of viral replication. Additionally, alterations in lipid metabolism, including enhanced fatty acid synthesis and disrupted cholesterol homeostasis, facilitate viral entry, replication, and immune evasion. The dysregulation of mitochondrial function and oxidative stress pathways also contributes to disease severity and long-term complications, such as persistent inflammation and immune exhaustion. Understanding these metabolic shifts is crucial for identifying new therapeutic targets and novel biomarkers for early disease detection, prognosis, and patient stratification. This review provides an overview of the metabolic alterations induced by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus, highlighting shared and virus-specific mechanisms and potential therapeutic interventions.

Keywords:  infectious diseases; influenza; metabolism; respiratory infections; respiratory syncytial virus; severe acute respiratory syndrome coronavirus 2; viral infections

DOI:  https://doi.org/10.3390/biom15071027
BMC Microbiol. 2025 Jul 25. 25(1): 452

An untargeted metabolomics analysis in feces and brain of Orthoflaviviruses-infected mice.

Zhiwei Su, Ningze Sun, Chenghong Yin, Xiaoyan Zheng.

  Annually, millions of people are affected by mosquito-borne Orthoflavivirus infections. These include diseases caused by the Dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), posing a formidable challenge to global public health. This research aims to explore the potential role of the Gut-Brain Axis (GBA) in Orthoflavivirus infection, particularly focusing on key metabolites involved in the process of viral invasion into the central nervous system. Given the advantages of metabolomics technology in metabolite identification. Therefore, we employed an untargeted Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics platform to examine alterations in metabolite concentrations within the feces and brain tissues of mice infected with DENV, JEV, or ZIKV, as well as uninfected controls. The results showed that 225, 240, and 252 differential metabolites were identified in the fecal metabolome of DENV, JEV, and ZIKV infections, respectively, with amino acid metabolism and lipid metabolism being significantly disrupted. In the brain metabolome, 37, 81, and 18 differential metabolites were identified for DENV, JEV, and ZIKV infections, respectively, with lipid metabolism and purine metabolism being significantly disrupted. Amino acids with low abundance in viral proteins are significantly disrupted in the amino acid metabolism pathway, suggesting that Orthoflaviviruses adapt to its needs for synthesizing viral proteins by regulating the host's amino acid composition. The disruption of purine metabolism also implies the viral genome replication process occurring in the brain. Moreover, the disturbance of lipid metabolism is highly correlated with the biological function of the Orthoflavivirus envelope, where Sphingosine 1-phosphate (S1P) may be the key for Orthoflaviviruses to enter the human central nervous system via the GBA. This research is the first to explore the potential role of GBA in Orthoflavivirus infection through joint metabolomic analysis of fecal and brain tissue samples, providing new insights into viral invasion of the central nervous system. The findings not only elucidate the characteristics of viral infection from complementary perspectives of fecal and brain tissue samples, revealing associated metabolic changes, but also establish a foundation for subsequent identification of biomarkers to diagnose disease states-particularly for predicting central nervous system infection risks. The specific patterns revealed by fecal metabolomics analysis provide the theoretical basis for developing non-invasive predictive approaches to assess brain infection status in the future.

Keywords:   Orthoflavivirus ; Biomarkers; GBA; LC-MS; Metabolomics

DOI:  https://doi.org/10.1186/s12866-025-04192-0
Vet Microbiol. 2025 Jul 16. pii: S0378-1135(25)00270-6. [Epub ahead of print]308 110635

Multi-omics profiling reveals infectious bursal disease virus-induced alterations in gene expression and metabolism in chicken bursa of fabricius.

Cuiping Song, Siyu Li, Yanmei Yuan, Wei Gao, Xusheng Qiu, Lei Tan, Yingjie Sun, Ning Tang, Yang Qu, Ying Liao, Chan Ding.

  Infectious Bursal Disease (IBD) is an acute, highly contagious disease caused by IBDV, characterized by inflammation, atrophy of the Bursa of Fabricius, and immunosuppression. This study infected 21-day-old SPF chickens with three IBDV strains (classical YZ, very virulent AH, and variant SD). On day 7 post-infection, bursa samples were collected for transcriptomic and metabolomic analyses. Metabolite profiles were analyzed using multivariate statistics, and KEGG enrichment analysis was used to identify dysregulated pathways, elucidating the transcriptional and metabolic responses in IBDV-infected bursa tissue. Transcriptomic analysis identified 1733 DEGs in the YZ group, 5731 in the AH group, and 84 in the SD group. Gene Ontology clustering of common SDE genes between virus-infected and control groups focused on cellular components, molecular functions, and biological processes；KEGG enrichment showed they were mainly involved in lipid-related metabolic pathways for the three IBDV subtypes. Metabolomic analysis detected 460 significantly changed metabolites per subtype after IBDV infection. Lipid metabolism disorders were associated with IBDV, involving L-carnitine and other substances；KEGG analysis indicated the main pathways were lipid-related, like arachidonic acid (AA) metabolism. Moreover, this study verified mRNA levels of cytokines, NLRP3 protein level, and AA content. IBDV infection induces differential gene expression related to host immune response and metabolic regulation at the transcriptomic level, with metabolomic changes mainly involving lipid metabolism. Integrating transcriptomics and metabolomics provides a comprehensive understanding of the host's response to IBDV infection.

Keywords:  Arachidonic acid; Infectious bursal disease virus; Metabolomics; NLRP3; Transcriptomics

DOI:  https://doi.org/10.1016/j.vetmic.2025.110635
Microorganisms. 2025 Jul 10. pii: 1633. [Epub ahead of print]13(7):

Significant Increase of Cinnamic Acid in Metabolites of Chicks Infected with Infectious Bronchitis Virus and Its Remarkable Antiviral Effects In Vitro and In Vivo.

Lan-Ping Wei, Tao-Ni Zhang, Yu Zhang, Li-Na Ren, Yan-Peng Lu, Tian-Chao Wei, Teng Huang, Jian-Ni Huang, Mei-Lan Mo.

  Avian infectious bronchitis virus (IBV) infection has caused significant economic losses to the poultry industry. Unfortunately, there is currently no effective cure for this disease. Understanding the pathogenic mechanism is crucial for the treatment of the disease. Studying the pathogenic mechanism of IBV based on metabolomics analysis is helpful for identifying antiviral drugs. However, studies on metabolomics analysis of IBV infection have been relatively limited, particularly without metabolomics analysis in sera after IBV infection. In this study, 17-day-old SPF chicks were infected with the IBV GX-YL5 strain, and serum samples were collected 7 days post-infection (DPI) for metabolomics analysis using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A total of 143 differential metabolites were identified across 20 metabolic pathways, with the phenylalanine pathway showing the most significant changes. The level of cinnamic acid (CA), an upstream metabolite in the phenylalanine pathway, was notably increased following IBV infection. To investigate the antiviral effects of CA, chicken embryo kidney (CEK) cells and SPF chicks infected with IBV were treated with different concentrations of CA to assess its effect on viral replication. The results demonstrated that CA at 25 μg/mL effectively inhibited IBV replication in vitro; meanwhile, CA at 50 μg/mL and 25 μg/mL effectively inhibited IBV replication in vivo. Molecular docking and molecular dynamics simulation studies showed that CA interacts with the N domains of the IBV nucleocapsid (N) protein. In conclusion, the serum metabolite CA is significantly elevated following IBV infection and demonstrates remarkable antiviral effects both in vitro and in vivo, providing a promising avenue for the development of antiviral therapies to combat IBV infection.

Keywords:  N protein; antiviral; cinnamic acid; infectious bronchitis virus; metabolomics

DOI:  https://doi.org/10.3390/microorganisms13071633
PLoS Pathog. 2025 Jul;21(7): e1013366

Lactylation and viral infections: A novel link between metabolic reprogramming and immune regulation.

Shanshan Chen, Tongxue Qin, Shengrui Luo, Fengyi Wang, Feirong Chen, Hailun Wei, Yuting Wu, Rongfeng Chen, Wudi Wei, Jingzhen Lai, Hao Liang, Li Ye, Zongxiang Yuan, Junjun Jiang.

Post-translational modifications (PTMs) regulate protein structure, function, and interactions, playing pivotal roles in cellular processes and disease progression. Lactate, a byproduct of the Warburg effect, accumulates excessively during viral infections and functions as a signaling molecule, disrupting mitochondrial antiviral-signaling protein activity and facilitating viral immune evasion. Lactylation, a recently identified PTM derived from lactate metabolism, links cellular metabolism and immune regulation by modulating gene expression and metabolic reprogramming. It also serves as a mechanism for viruses to modulate host immunity. Despite its emerging importance, its role with respect to viruses infecting humans and animals remains poorly understood. Investigating its impact on metabolic, protein modifications, and immune signaling may reveal novel immune evasion strategies and therapeutic targets. This review aims to provide an overview of the fundamental features and regulatory functions of lactylation, explore its association with viral infections, and offer insights into how lactylation influences metabolic and immune responses during virus-host interactions.

DOI: https://doi.org/10.1371/journal.ppat.1013366
Vet Res Commun. 2025 Aug 01. 49(5): 270

Metabolomic evidence of bovine leukemia virus regulation on ferroptosis in bovine mammary epithelial cells.

Shuai Lian, Xiujuan Zheng, Miao Yu, Zijian Geng, Jianfa Wang, Guanxin Lv, Di Wang.

  Bovine leukemia virus (BLV) is a globally prevalent pathogen that can cause enzootic bovine leukosis (EBL), which reduces dairy cows' immunity, interferes with mammary antimicrobial defense capabilities, and exacerbates clinical mastitis. However, the specific mechanisms by which these effects occur remain incompletely understood. Ferroptosis, an iron-dependent non-apoptotic cell death mechanism, exhibits dual roles in viral infections. In this study, wild-type BLV and a miRNA-deficient mutant strain (BLV-ΔmiRNA) were used to infect bovine mammary epithelial cells in vitro, combined with non-targeted metabolomics to investigate BLV-regulated ferroptosis evidence. The results shown that BLV significantly elevated levels of unsaturated fatty acid, interferes with vitamin B6 metabolism. Suggest that BLV promote ferroptosis in mammary epithelial cells through unsaturated fatty acid biosynthesis and vitamin B6 metabolism pathways, potentially involving BLV-encoded miRNAs. This research provides a theoretical foundation for identifying novel BLV pathogenic targets and prevention strategies.

Keywords:  Bovine leukemia virus; Bovine mammary epithelial cells; Ferroptosis; Metabolomics

DOI:  https://doi.org/10.1007/s11259-025-10840-7
J Cell Mol Med. 2025 Jul;29(14): e70722

HBx Drives Liver Cancer Stem Cell Generation Through Stimulating Glucose Metabolic Reprogramming.

Jinchen Liu, Xueqin Wu, Qiushi Yin, Luying Zhang, Kun Liu, Kailin Huang, Junnv Xu, Xiaowei Li, Bo Lin, Mingyue Zhu, Mengsen Li.

  Recurrence of hepatocellular carcinoma (HCC) is closely related to the infection of hepatitis B virus (HBV). The HBV x protein (HBx) plays a key role in promoting the malignant transformation of hepatocytes and cancer heterogeneity, but the role of HBx in metabolism influencing the generation of cancer stem cells (CSCs) is still unclear. This study explores HBx-induced glucose metabolic reprogramming of HCC cells to promote the generation of CSCs. Immunohistochemical analysis of the expression of glucose metabolic reprogramming-related enzymes and stemness markers in HCC tissues and corresponding paracancer tissues of 30 patients; Western blotting, laser confocal microscopy, and metabolism-detection kits were applied to analyse the expression of glucose metabolism-related enzymes and cancer stemness markers and glucose metabolic products; the generation of CSCs was observed by stem cell pellet and soft agar colony formation experiments. Results indicated that the expression of PKM2, HK2, LDHA, CSC-related proteins, and CD133 and CD44 in HCC tissues was significantly higher than that in the corresponding paracancerous tissues. HBx stimulated the expression of the key enzyme of the Warburg effect and CSC-related proteins, and these proteins were significantly reduced after interference with the expression of the PKM2 protein. PKM2 and OCT4 interact in HCC cells, and PKM2 has a regulatory effect on OCT4 function. This study found that HBx stimulated the Warburg effect and induced HCC stemness reprogramming by activating the PI3K/AKT signalling pathway; PKM2 played a key role in promoting the initiation of HCC stem cells. Targeting HBx and PKM2 is a new strategy for the treatment of HCC.

Keywords:   HBx ; Warburg effect; cancer stem cells; glucose metabolism reprogramming; hepatocellular carcinoma

DOI:  https://doi.org/10.1111/jcmm.70722
Am J Respir Cell Mol Biol. 2025 Jul 28.

ER Stress Disrupts the Airway Epithelium and Reduces Host Defense during Influenza A Virus Infection.

Erin Y Earnhardt, Jennifer L Tipper, Mohamed A Hanafy, Ahmed Lazrak, Abel Lopez, Sarah E Perritt, David C LaFon, James A Mobley, George M Solomon, Kevin S Harrod.

  Secondary Streptococcus pneumoniae (Spn) infection to influenza A virus (IAV) frequently leads to an increase in morbidity and mortality of IAV. Our recent work establishes that IAV infection disrupts bacterial host defense in the lung epithelium through loss of cystic fibrosis transmembrane conductance regulator protein (CFTR) function, causing an acidification of the ASL and subsequently increasing susceptibility to Spn. Infection with IAV and other respiratory pathogens cause a robust endoplasmic reticulum (ER) stress response. However, the role of this acute ER stress response in predisposing the airway epithelium to susceptibility to bacterial infections remains unknown. Utilizing a primary differentiated human bronchial airway epithelial cell (HBEC) culture system, we find that both IAV-induced ER stress and ER stress alone increase susceptibility to Spn in the airway epithelium and lead to a loss of CFTR activity, subsequently causing a disruption in the rheostatic properties of the airway surface liquid. Importantly, in HBECs without functional CFTR, modulation of ER stress in the presence and absence IAV of has no effect on susceptibility to Spn. Restoration of ASL pH after ER stress in HBECs with functional CFTR reduces Spn, suggesting that ER stress increases susceptibility to bacterial infection by disrupting CFTR and causing an acidification of the ASL. Here, we demonstrate a clear role for ER stress in disruption of both the airway epithelium and bacterial host defense mechanisms during respiratory viral infection.

Keywords:  Cell stress; Influenza; Viruses; airways; cystic fibrosis

DOI:  https://doi.org/10.1165/rcmb.2025-0141OC