bims-mevinf Biomed News
on Metabolism in viral infections
Issue of 2024–04–14
five papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology
  1. Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies.
  2. Metabolomics analysis of CEF cells infected with avian leukosis virus subgroup J based on UHPLC-QE-MS.
  3. Metformin Inhibits Zika Virus Infection in Trophoblast Cell Line.
  4. Glycolysis is reduced in dengue virus 2 infected liver cells.
  5. Oxidative Stress Markers and Histopathological Changes in Selected Organs of Mice Infected with Murine Norovirus 1 (MNV-1).
  1. ACS Omega. 2024 Apr 02. 9(13): 15535-15546
    Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies.
    Mustafa Sertbas, Kutlu O Ulgen.
      Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host-virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on liver metabolism was investigated using integrated GEMs of human hepatocytes and SARS-CoV-2. They were generated for uninfected and infected hepatocytes using transcriptome data. Reporter metabolite analysis resulted in significant transcriptional changes around several metabolites involved in xenobiotics, drugs, arachidonic acid, and leukotriene metabolisms due to SARS-CoV-2 infection. Flux balance analysis and minimization of metabolic adjustment approaches unraveled possible virus-induced hepatocellular reprogramming in fatty acid, glycerophospholipid, sphingolipid cholesterol, and folate metabolisms, bile acid biosynthesis, and carnitine shuttle among others. Reaction knockout analysis provided critical reactions in glycolysis, oxidative phosphorylation, purine metabolism, and reactive oxygen species detoxification subsystems. Computational analysis also showed that administration of dopamine, glucosamine, D-xylose, cysteine, and (R)-3-hydroxybutanoate contributes to alleviating viral infection. In essence, the reconstructed host-virus GEM helps us understand metabolic programming and develop therapeutic strategies to battle SARS-CoV-2.
    DOI:  https://doi.org/10.1021/acsomega.4c00392
  2. Poult Sci. 2024 Mar 28. pii: S0032-5791(24)00274-8. [Epub ahead of print]103(6): 103693
    Metabolomics analysis of CEF cells infected with avian leukosis virus subgroup J based on UHPLC-QE-MS.
    Menglu Xu, Kun Qian, Hongxia Shao, Yongxiu Yao, Venugopal Nair, Jianqiang Ye, Aijian Qin.
      Avian leukosis virus subgroup J (ALV-J) is a retrovirus that can cause immunosuppression and tumors in chicken. However, relative pathogenesis is still not clear. At present, metabolomics has shown great potential in the screening of tumor metabolic markers, prognostic evaluation, and drug target design. In this study, we utilize an untargeted metabolomics approach based on ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) to analyze the metabolic changes in chicken embryo fibroblast (CEF) cells infected by ALV-J. We found that ALV-J infection significantly altered a wealth of metabolites compared with control group. Additionally, most of the differentially expressed metabolites belonged to lipid metabolism, purine nucleotide metabolism and amino acid metabolism. Among them, the proportion of lipid metabolites account for the highest proportion (around 31%). Results suggest that these changes may be conductive to the formation of virion, thereby promoting the replication of ALV-J. These data provided metabolic evidence and potential biomarkers for the cellular metabolic changes induced by ALV-J, and provided important insight for further understanding the replication needs and pathogenesis of ALV-J.
    Keywords:  CEF cell; avian leukosis virus subgroup J; lipid; metabolite
    DOI:  https://doi.org/10.1016/j.psj.2024.103693
  3. Curr Microbiol. 2024 Apr 09. 81(5): 133
    Metformin Inhibits Zika Virus Infection in Trophoblast Cell Line.
    Manuel Adrían Velazquez-Cervantes, Orestes López-Ortega, Victor Javier Cruz-Holguín, Luis Herrera Moro-Huitron, Arturo Flores-Pliego, Ignacio Lara-Hernandez, Mauricio Comas-García, Oscar Villavicencio-Carrisoza, Addy Cecilia Helguera-Reppeto, Haruki Arévalo-Romero, Edgar Ricardo Vázquez-Martínez, Moises León-Juárez.
      Zika virus (ZIKV) infections have been associated with severe clinical outcomes, which may include neurological manifestations, especially in newborns with intrauterine infection. However, licensed vaccines and specific antiviral agents are not yet available. Therefore, a safe and low-cost therapy is required, especially for pregnant women. In this regard, metformin, an FDA-approved drug used to treat gestational diabetes, has previously exhibited an anti-ZIKA effect in vitro in HUVEC cells by activating AMPK. In this study, we evaluated metformin treatment during ZIKV infection in vitro in a JEG3-permissive trophoblast cell line. Our results demonstrate that metformin affects viral replication and protein synthesis and reverses cytoskeletal changes promoted by ZIKV infection. In addition, it reduces lipid droplet formation, which is associated with lipogenic activation of infection. Taken together, our results indicate that metformin has potential as an antiviral agent against ZIKV infection in vitro in trophoblast cells.
    DOI:  https://doi.org/10.1007/s00284-024-03651-7
  4. Sci Rep. 2024 04 09. 14(1): 8355
    Glycolysis is reduced in dengue virus 2 infected liver cells.
    Chanida Chumchanchira, Suwipa Ramphan, Wannapa Sornjai, Sittiruk Roytrakul, Pathrapol Lithanatudom, Duncan R Smith.
      Infections with dengue virus (DENV) remain a worldwide public health problem. A number of bona fide cellular targets of DENV have been identified including liver cells. Despite the many lines of evidence confirming the involvement of hepatocytes during DENV infection, only a few studies have used proteomic analysis to understand the modulation of the cellular proteome occurring upon DENV infection. We utilized a 2D-gel electrophoresis analysis to identify proteins that were differentially regulated by DENV 2 infection of liver (Hep3B) cells at 12 h post infection (hpi) and at 48 hpi. The analysis identifies 4 proteins differentially expressed at 12 hpi, and 14 differentially regulated at 48 hpi. One candidate protein identified as downregulated at 48 hpi in the proteomic analysis (GAPDH) was validated in western blotting in Hep3B cells, and subsequently in induced pluripotent stem cell (iPSC) derived human hepatocytes. The reduced expression of GAPDH was coupled with an increase in NADH, and a significantly reduced NAD + /NADH ratio, strongly suggesting that glycolysis is down regulated in response to DENV 2 infection. Metformin, a well characterized drug used in the treatment of diabetes mellitus, is an inhibitor of hepatic gluconeogenesis was shown to reduce the level of DENV 2 infection and new virus production. Collectively these results show that although glycolysis is reduced, glucose is still required, possibly for use by the pentose phosphate pathway to generate nucleosides required for viral replication.
    DOI:  https://doi.org/10.1038/s41598-024-58834-w
  5. Int J Mol Sci. 2024 Mar 23. pii: 3614. [Epub ahead of print]25(7):
    Oxidative Stress Markers and Histopathological Changes in Selected Organs of Mice Infected with Murine Norovirus 1 (MNV-1).
    Paulina Janicka, Dominika Stygar, Elżbieta Chełmecka, Piotr Kuropka, Arkadiusz Miążek, Aleksandra Studzińska, Aleksandra Pogorzelska, Katarzyna Pala, Barbara Bażanów.
      This paper describes the effects of murine norovirus (MNV) infection on oxidative stress and histopathological changes in mice. This study uses histopathological assays, enzymatic and non-enzymatic antioxidant markers, and total oxidative status and capacity (TOS, TAC). The results suggest that MNV infection can lead to significant changes with respect to the above-mentioned parameters in various organs. Specifically, reduced superoxide dismutase (SOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione reductase (GR) activities were observed in liver tissues, while higher MnSOD activity was observed in kidney tissues of MNV-infected mice when compared to the control. GR activity was lower in all tissues of MNV-infected mice tested, with the exception of lung tissue. This study also showed that norovirus infection led to increased TOS levels in the brain and liver and TAC levels in the brain, while TOS levels were significantly reduced in the kidneys. These changes may be due to the production of reactive oxygen species (ROS) caused by the viral infection. ROS can damage cells and contribute to oxidative stress. These studies help us to understand the pathogenesis of MNV infection and its potential effects on oxidative stress and histopathological changes in mice, and pave the way for further studies of the long-term effects of MNV infection.
    Keywords:  bacterial and viral diseases; oxidative stress
    DOI:  https://doi.org/10.3390/ijms25073614
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