Viruses and Cellular Metabolism 2023

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 13894

Special Issue Editors


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Guest Editor
1. INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69003 Lyon, France
2. Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, 69434 Lyon, France
Interests: viral hepatitis; metabolism; chronic liver disease; liver cancer
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Guest Editor
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
Interests: hepatitis virus; SARS-CoV-2; influenza virus; metabolomics; polyamines; antiviral agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

The regulation of metabolic pathways is tightly linked to cell growth and differentiation. A wide spectrum of pathologies is associated with the disturbance of specific metabolic pathways and changes in the intracellular pools of the respective metabolites. These pathologies include cancer, inflammatory and autoimmune diseases, endocrine disorders, and non-bacterial infections. Cell metabolism is also closely linked to the production and scavenging of reactive oxygen species (ROS), as ROS control redox-dependent transcription factors and the expression of many metabolic enzymes; however, the interplay between viral infections with the metabolism of a host cell has overall been explored to a far lesser extent. Nevertheless, there are data that show that both DNA and RNA viruses interfere with central carbon metabolism as well as the biosynthesis and degradation of amino acids, lipids, and biogenic polyamines. Finally, markers of changes in metabolic and redox systems correlate with the development of some virus-associated diseases.

In this Special Issue we would like to bring together original research papers, short communications, and review articles on the interplay between viral infections with metabolic and redox pathways in infected cells, tissues, and organisms. Specifically, we seek papers that focus on the following:

  1. Changes in cell metabolism that occur in viral infections.
  2. Interplay between viruses and redox pathways.
  3. Role of cellular metabolites in the replication of viruses.
  4. Altered metabolism and redox status as triggers of virus-induced pathogenesis.
  5. Metabolites as biomarkers for virus-associated diseases.
  6. Inhibitors of metabolic enzymes as antivirals.
  7. Modulation of cytopathic/oncolytic activity of viruses by targeting cell metabolism.
  8. Technical perspectives for virologists working in the fields of metabolomics and redox biology.

Dr. Birke Bartosch
Dr. Alexander Ivanov
Guest Editors

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Keywords

  • RNA viruses
  • DNA viruses
  • metabolomics
  • redox biology
  • pathogenesis
  • carcinogenesis
  • inflammation
  • fibrosis

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Published Papers (7 papers)

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Research

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13 pages, 4239 KiB  
Article
The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals
by Maria Alice Freitas Queiroz, Allysson Quintino Tenório de Oliveira, Tuane Carolina Ferreira Moura, Wandrey Roberto dos Santos Brito, Emmanuelle Giuliana Mendes Santana, Lorena Leticia Peixoto de Lima, Felipe Teixeira Lopes, Carlos David Araújo Bichara, Ednelza da Silva Graça Amoras, Ricardo Ishak, Izaura Maria Vieira Cayres Vallinoto and Antonio Carlos Rosário Vallinoto
Viruses 2024, 16(4), 499; https://doi.org/10.3390/v16040499 - 25 Mar 2024
Viewed by 2141
Abstract
TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and [...] Read more.
TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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14 pages, 881 KiB  
Article
Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants
by Louise D. V. du Toit, Shayne Mason, Mari van Reenen, Theresa M. Rossouw and Roan Louw
Viruses 2024, 16(2), 313; https://doi.org/10.3390/v16020313 - 19 Feb 2024
Cited by 1 | Viewed by 1792
Abstract
HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between [...] Read more.
HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using 1H-NMR spectroscopy on maternal plasma at 28 weeks’ gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants’ plasma metabolites involved in energy utilization, growth, and protection from infection. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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29 pages, 4503 KiB  
Article
HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype
by Alla Zhitkevich, Ekaterina Bayurova, Darya Avdoshina, Natalia Zakirova, Galina Frolova, Sona Chowdhury, Alexander Ivanov, Ilya Gordeychuk, Joel M. Palefsky and Maria Isaguliants
Viruses 2024, 16(2), 193; https://doi.org/10.3390/v16020193 - 26 Jan 2024
Cited by 1 | Viewed by 2120 | Correction
Abstract
The high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not fully understood. A collaboration between [...] Read more.
The high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not fully understood. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells has long been anticipated. Here, we delineated the effects of HIV-1 reverse transcriptase on the in vitro and in vivo properties of HPV16-infected cervical cancer cells. A human cervical carcinoma cell line infected with HPV16 (Ca Ski) was made to express HIV-1 reverse transcriptase (RT) by lentiviral transduction. The levels of the mRNA of the E6 isoforms and of the factors characteristic to the epithelial/mesenchymal transition were assessed by real-time RT-PCR. The parameters of glycolysis and mitochondrial respiration were determined using Seahorse technology. RT expressing Ca Ski subclones were assessed for the capacity to form tumors in nude mice. RT expression increased the expression of the E6*I isoform, modulated the expression of E-CADHERIN and VIMENTIN, indicating the presence of a hybrid epithelial/mesenchymal phenotype, enhanced glycolysis, and inhibited mitochondrial respiration. In addition, the expression of RT induced phenotypic alterations impacting cell motility, clonogenic activity, and the capacity of Ca Ski cells to form tumors in nude mice. These findings suggest that HIV-RT, a multifunctional protein, affects HPV16-induced oncogenesis, which is achieved through modulation of the expression of the E6 oncoprotein. These results highlight a complex interplay between HIV antigens and HPV oncoproteins potentiating the malignant transformation of epithelial cells. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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11 pages, 773 KiB  
Communication
Polymorphisms Related to Iron Homeostasis Associate with Liver Disease in Chronic Hepatitis C
by Anna Wróblewska, Anna Woziwodzka, Magda Rybicka, Krzysztof P. Bielawski and Katarzyna Sikorska
Viruses 2023, 15(8), 1710; https://doi.org/10.3390/v15081710 - 9 Aug 2023
Cited by 2 | Viewed by 1771
Abstract
Dysregulation of iron metabolism in chronic hepatitis C (CHC) is a significant risk factor for hepatic cirrhosis and cancer. We studied if known genetic variants related to iron homeostasis associate with liver disease progression in CHC. Retrospective analysis included 249 CHC patients qualified [...] Read more.
Dysregulation of iron metabolism in chronic hepatitis C (CHC) is a significant risk factor for hepatic cirrhosis and cancer. We studied if known genetic variants related to iron homeostasis associate with liver disease progression in CHC. Retrospective analysis included 249 CHC patients qualified for antiviral therapy between 2004 and 2014. For all patients, nine SNPs within HFE, TFR2, HDAC2, HDAC3, HDAC5, TMPRSS6, and CYBRD1 genes were genotyped. Expression of selected iron–related genes, was determined with qRT-PCR in 124 liver biopsies, and mRNA expression of co-inhibitory receptors (PD-1, Tim3, CTLA4) was measured in 79 liver samples. CYBRD1 rs884409, HDAC5 rs368328, TFR2 rs7385804, and TMPRSS6 rs855791 associated with histopathological changes in liver tissue at baseline. The combination of minor allele in HDAC3 rs976552 and CYBRD1 rs884409 linked with higher prevalence of hepatocellular carcinoma (HCC) during follow up (OR 8.1 CI 2.2–29.2; p = 0.001). Minor allele in HDAC3 rs976552 associated with lower hepatic expression of CTLA4. Tested polymorphisms related to iron homeostasis associate with histopathological changes in the liver. The presence of both HDAC3 rs976552 G and CYBRD1 rs884409 G alleles correlates with HCC occurrence, especially in the group of patients with elevated AST (>129 IU/L). rs976552 in HDAC3 could impact immunological processes associated with carcinogenesis in CHC. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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17 pages, 4074 KiB  
Article
ICP4-Associated Activation of Rap1b Facilitates Herpes Simplex Virus Type I (HSV-1) Infection in Human Corneal Epithelial Cells
by Beibei Zhang, Juntao Ding and Zhenghai Ma
Viruses 2023, 15(7), 1457; https://doi.org/10.3390/v15071457 - 27 Jun 2023
Viewed by 1733
Abstract
The strong contribution of RAS-related protein 1b (Rap1b) to cytoskeleton remodeling determines intracellular and extracellular physiological activities, including the successful infection of viruses in permissive cells, but its role in the HSV-1 life cycle is still unclear. Here, we demonstrated that the HSV-1 [...] Read more.
The strong contribution of RAS-related protein 1b (Rap1b) to cytoskeleton remodeling determines intracellular and extracellular physiological activities, including the successful infection of viruses in permissive cells, but its role in the HSV-1 life cycle is still unclear. Here, we demonstrated that the HSV-1 immediate early (IE) gene ICP4 inhibits protein kinase A (PKA) phosphorylation to induce Rap1b-activation-mediated viral infection. Rap1b activation and membrane enrichment begin at the early stage of HSV-1 infection and remain active during the proliferation period of the virus. Treating the cells with Rap1b small interfering RNA (siRNA) showed a dose-dependent decrease in viral infection levels, but no dose-dependent increase was observed after Rap1b overexpression. Further investigation indicated that the suppression of Rap1b activation derives from phosphorylated PKA and Rap1b mutants with partial or complete prenylation instead of phosphorylation, which promoted viral infection in a dose-dependent manner. Furthermore, the PKA agonist Forskolin disturbed Rap1b activation in a dose-dependent manner, accompanied by a decreasing trend in viral infection. Moreover, the HSV-1 IE gene ICP4 induced PKA dephosphorylation, leading to continuous Rap1b activation, followed by cytoskeleton rearrangement induced by cell division control protein 42 (CDC42) and Ras-related C3 botulinum toxin substrate 1 (RAC1). These further stimulated membrane-triggered physiological processes favoring virus infection. Altogether, we show the significance of Rap1b during HSV-1 infection and uncover the viral infection mechanism determined by the posttranslational regulation of the viral ICP4 gene and Rap1b host protein. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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Review

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25 pages, 3108 KiB  
Review
Metabolic Enzymes in Viral Infection and Host Innate Immunity
by Chao Qin, Taolin Xie, Wayne Wei Yeh, Ali Can Savas and Pinghui Feng
Viruses 2024, 16(1), 35; https://doi.org/10.3390/v16010035 - 24 Dec 2023
Cited by 1 | Viewed by 2681
Abstract
Metabolic enzymes are central players for cell metabolism and cell proliferation. These enzymes perform distinct functions in various cellular processes, such as cell metabolism and immune defense. Because viral infections inevitably trigger host immune activation, viruses have evolved diverse strategies to blunt or [...] Read more.
Metabolic enzymes are central players for cell metabolism and cell proliferation. These enzymes perform distinct functions in various cellular processes, such as cell metabolism and immune defense. Because viral infections inevitably trigger host immune activation, viruses have evolved diverse strategies to blunt or exploit the host immune response to enable viral replication. Meanwhile, viruses hijack key cellular metabolic enzymes to reprogram metabolism, which generates the necessary biomolecules for viral replication. An emerging theme arising from the metabolic studies of viral infection is that metabolic enzymes are key players of immune response and, conversely, immune components regulate cellular metabolism, revealing unexpected communication between these two fundamental processes that are otherwise disjointed. This review aims to summarize our present comprehension of the involvement of metabolic enzymes in viral infections and host immunity and to provide insights for potential antiviral therapy targeting metabolic enzymes. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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Other

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2 pages, 138 KiB  
Correction
Correction: Zhitkevich et al. HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype. Viruses 2024, 16, 193
by Alla Zhitkevich, Ekaterina Bayurova, Darya Avdoshina, Natalia Zakirova, Galina Frolova, Sona Chowdhury, Alexander Ivanov, Ilya Gordeychuk, Joel M. Palefsky and Maria Isaguliants
Viruses 2024, 16(4), 589; https://doi.org/10.3390/v16040589 - 11 Apr 2024
Viewed by 832
Abstract
Author Juris Jansons requested his exclusion from the authors of the original publication [...] Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism 2023)
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