bims-mevinf Biomed News
on Metabolism in viral infections
Issue of 2025–01–05
five papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology
  1. Manganese is a potent inducer of lysosomal activity that inhibits de novo HBV infection.
  2. Determination of oxidative stress and copeptin levels of COVID-19 according to the clinical course.
  3. Host lipid metabolism influences the variation in resistance of Pekin ducks to duck hepatitis A virus genotype 3.
  4. Transcriptomic and metabolomic analyses reveal the spatial role of carnitine metabolism in the progression of hepatitis B virus cirrhosis to hepatocellular carcinoma.
  5. Placentas From SARS-CoV-2 Infection During Pregnancy Exhibit Foci of Oxidative Stress and DNA Damage.
  1. PLoS Pathog. 2025 Jan;21(1): e1012800
    Manganese is a potent inducer of lysosomal activity that inhibits de novo HBV infection.
    Lin Yu, Hao Chang, Wentao Xie, Yuan Zheng, Le Yang, Qiong Wu, Fan Bu, Yuanfei Zhu, Youhua Xie, Guoyu Pan, Ke Lan, Qiang Deng.
      Sodium taurocholate co-transporting polypeptide (NTCP) has been identified as an entry receptor for hepatitis B virus (HBV), but the molecular events of the viral post-endocytosis steps remain obscure. In this study, we discovered that manganese (Mn) could strongly inhibit HBV infection in NTCP-reconstituted HepG2 cells without affecting viral replication. We therefore profiled the antiviral effects of Mn2+ in an attempt to elucidate the regulatory mechanisms involved in early HBV infection. Intriguingly, Mn2+ conspicuously stimulated lysosomal activity, as evidenced by hyperactivation of mTORC1 and increased endo/lysosomal acidity. After HBV-triggered internalization, the NTCP receptor was sorted to late endosomal compartments by the ESCRT machinery in concert with the invading virion. The establishment of HBV infection was found to be independent of lysosomal fusion-driven late endosome maturation; Mn2+-induced lysosomal hyperfunction virtually impaired infection, suggesting that virions may gain cytosolic access directly from late endosomes. In contrast, suppression of lysosomal activity substantially enhanced HBV infection. Prolonged mTORC1 inactivation facilitated viral infection by depleting lysosomes and accelerating endocytic transport of virions. Notably, treatment with the natural steroidal alkaloid tomatidine recapitulated the effects of Mn2+ in stimulating lysosomal activity and exhibited potent anti-HBV activity in HepG2-NTCP cells and in proliferating human hepatocyte organoids. These findings provide new insights into the post-endocytosis events of HBV infection. The negative regulation of early HBV infection by endo/lysosomal activity makes it a promising target for antiviral therapies.
    DOI:  https://doi.org/10.1371/journal.ppat.1012800
  2. Microb Pathog. 2024 Dec 28. pii: S0882-4010(24)00730-7. [Epub ahead of print]199 107263
    Determination of oxidative stress and copeptin levels of COVID-19 according to the clinical course.
    Marwa Abdelmageed, Figen Güzelgül, Serap Yalin, Merih Akkapulu.
       OBJECTIVE: COVID-19, caused by the novel coronavirus SARS-CoV-2, is characterized by hyperinflammation, which can trigger oxidative stress. At the same time, COVID-19 is accompanied by both psychological and physical stress. Copeptin, a novel stress marker, has been shown to predict disease outcomes in stress-induced diseases. In this study, we aimed to explore the potential of copeptin, with inflammatory and oxidative stress markers, in distinguishing between different clinical courses of COVID-19.
    MATERIALS AND METHODS: This case-control study included 75 participants: 25 COVID-19 patients hospitalized in the intensive care unit (ICU), 25 non-ICU COVID-19 patients, and 25 healthy individuals. 64 % of the ICU patients received corticosteroid treatment for 4-10 days before sampling. Serum concentrations of the study parameters were assessed by enzyme-linked immunosorbent assay (ELISA) and compared between the study groups.
    RESULTS: Serum IL-6 levels (p < 0.001) were significantly higher in ICU patients compared to non-ICU patients and the control group. Serum MDA (p < 0.001) and 4-HNE (p = 0.027) concentrations were significantly lower in the ICU group in comparison with the other groups. Copeptin was not statistically significant. MDA (p = 0.040) and 4-HNE (p = 0.017) levels were significantly lower in the treated ICU group than the untreated one.
    CONCLUSIONS: Serum IL-6 levels were noticeably associated with COVID-19 severity. Corticosteroid therapy administration seemed to influence MDA and 4-HNE levels in the treated group, with no obvious influence on IL-6 and copeptin in the same cohort. This data suggests that in SARS-CoV-2 infection, corticosteroids may act through a rapid non-genomic mechanism.
    Keywords:  COVID-19; Copeptin; Corticosteroids; Inflammation; Oxidative stress
    DOI:  https://doi.org/10.1016/j.micpath.2024.107263
  3. Int J Biol Macromol. 2024 Dec 27. pii: S0141-8130(24)09979-3. [Epub ahead of print] 139168
    Host lipid metabolism influences the variation in resistance of Pekin ducks to duck hepatitis A virus genotype 3.
    Suyun Liang, Zhuo Chang, Meixi Lu, Zhanbao Guo, Dawei Luo, Guangnan Xing, Ming Xie, Wei Huang, Shuisheng Hou.
      Duck viral hepatitis (DVH) is a common and serious acute infectious disease that has a significantly impact on the duck farming industry. Duck hepatitis A virus type 3 (DHAV-3) is the major causative agent of DVH in East Asia. Host factor indicators of resistance to DHAV-3 in Pekin ducks were investigated using resistant (Z7R) and susceptible (Z7S) duck lines. Before DHAV-3 infection, Z7R had significantly higher HDL-C and LDL-C levels than Z7S. The results of population verification showed that Pekin ducks with HDL-C and/or LDL-C concentrations within their maximum 5 % confidence interval were highly resistant to DHAV-3. RNA-seq identified fifteen differentially expressed genes, primarily involved in lipid metabolism. Additionally, lipidomics identified one hundred distinct metabolites involved in glycerophospholipid metabolism. The ACSL6 gene was found to be significantly associated with OAHFA, PC, and PE. ACSL6, PE, PC, HDLC, and LDL-C co-regulated hepatic lipid metabolism. In conclusion, our results reveal that HDL-C and LDL-C may serve as markers of anti-DHAV-3 infection and lipid metabolism may be related to a potential mechanism of antiviral activity in Pekin ducks, providing a theoretical basis for future studies on the interaction between lipid metabolism and DHAV-3.
    Keywords:  DHAV-3; Lipid metabolism; Pekin duck
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139168
  4. Front Microbiol. 2024 ;15 1461456
    Transcriptomic and metabolomic analyses reveal the spatial role of carnitine metabolism in the progression of hepatitis B virus cirrhosis to hepatocellular carcinoma.
    Pengxiang Gao, Qiuping Liu, Ziye Luo, Wenjun Pu.
       Introduction: Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) resulting from chronic hepatitis B virus (HBV) infection are major health concerns. Identifying critical biomarkers and molecular targets is needed for early diagnosis, prognosis, and therapy of these diseases.
    Methods: In this study, we explored the gene expression and metabolism in the liver tissues of LC, HCC, and healthy controls, to analyse and identify potential biomarkers of disease progression. Mass spectrometry imaging was used to evaluate the spatial distribution of key metabolites.
    Results and discussion: The results revealed significant changes in gene expression and metabolic pathways along with disease progression. The upregulated genes were associated with extracellular matrix remodeling and cancer pathways, including LAMC1-3, COL9A2, COL1A1, MYL9, MYH11, and KAT2A. The downregulated genes were linked to immune response and fatty acid metabolism. Metabolomic analysis showed major changes in lipid and choline metabolism. Consistent changes in the expression of specific genes and metabolites were correlated with clinical data. Notably, metabolites such as L-acetylcarnitine, histamine, and 4-trimethylammoniobutanoic acid demonstrated high accuracy (AUC > 0.85) in distinguishing between healthy, LC, and HCC groups. This study identifies key gene and metabolite changes in HBV related LC and HCC, highlighting critical pathways involved in disease progression. Biomarkers like L-acetylcarnitine and KAT2A show promise for early diagnosis and prognosis, potentially improving outcomes for hepatitis liver disease patients.
    Keywords:  carnitine metabolism; hepatitis B virus; hepatocellular carcinoma; liver cirrhosis; mass spectrometry imaging; metabolomic; transcriptomic
    DOI:  https://doi.org/10.3389/fmicb.2024.1461456
  5. Am J Reprod Immunol. 2025 Jan;93(1): e70034
    Placentas From SARS-CoV-2 Infection During Pregnancy Exhibit Foci of Oxidative Stress and DNA Damage.
    Guilherme M Nobrega, Eliza R McColl, Arthur Antolini-Tavares, Renato T Souza, José Guilherme Cecatti, Maria Laura Costa, Indira U Mysorekar.
       PROBLEM: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.
    METHOD OF STUDY: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 term, 4 preterm) compared to uninfected controls (n = 10 term, 3 preterm). The placentas were analyzed for SARS-CoV-2 infection (spike and nucleocapsid viral proteins), markers of DNA damage (γH2AX) and oxidative stress (ROS), and senescence (telomere length, cell cycle regulators, and senescence-associated secretory phenotype [SASP]).
    RESULTS: Although no overall differences in cellular senescence markers were observed between the COVID-19 positive and negative groups, we found increased secreted SASP markers. Confocal microscopy of placentas from COVID-19 positive cases revealed localized areas of oxidative stress and DNA damage colocalized with SARS-CoV-2 spike protein.
    CONCLUSIONS: These findings indicate that SARS-CoV-2 infection induces localized focal placental damage, warranting further investigation into its impact on maternal and perinatal outcomes.
    Keywords:  COVID‐19; DNA damage; SARS‐CoV‐2; cell damage; cellular senescence; reactive oxygen species
    DOI:  https://doi.org/10.1111/aji.70034
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