Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection
Interferons (IFNs) are an essential part of innate immunity and contribute to adaptive immune responses. Here, we employed a loss-of-function analysis with human A549 respiratory epithelial cells with a knockout (KO) of the type I IFN receptor (IFNAR KO), either solely or together with the receptor...
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MDPI AG
2022-05-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/5/537 |
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| author | Erik Schilling Maria Elisabeth Wald Juliane Schulz Lina Emilia Werner Claudia Claus |
| author_facet | Erik Schilling Maria Elisabeth Wald Juliane Schulz Lina Emilia Werner Claudia Claus |
| author_sort | Erik Schilling |
| collection | DOAJ |
| description | Interferons (IFNs) are an essential part of innate immunity and contribute to adaptive immune responses. Here, we employed a loss-of-function analysis with human A549 respiratory epithelial cells with a knockout (KO) of the type I IFN receptor (IFNAR KO), either solely or together with the receptor of type III IFN (IFNAR/IFNLR1 KO). The course of rubella virus (RuV) infection on the IFNAR KO A549 cells was comparable to the control A549. However, on the IFNAR/IFNLR1 KO A549 cells, both genome replication and the synthesis of viral proteins were significantly enhanced. The generation of IFN β during RuV infection was influenced by type III IFN signaling. In contrast to IFNAR KO A549, extracellular IFN β was not detected on IFNAR/IFNLR1 KO A549. The bioenergetic profile of RuV-infected IFNAR/IFNLR1 KO A549 cells generated by extracellular flux analysis revealed a significant increase in glycolysis, whereas mitochondrial respiration was comparable between all three cell types. Moreover, the application of the glucose analogue 2-deoxy-D-glucose (2-DG) significantly increased viral protein synthesis in control A549 cells, while no effect was noted on IFNAR/IFNLR KO A549. In conclusion, we identified a positive signaling circuit of type III IFN signaling on the generation of IFN β during RuV infection and an IFN signaling-dependent contribution of glycolysis to RuV infection. This study on epithelial A549 cells emphasizes the interaction between glycolysis and antiviral IFN signaling and notably, the antiviral activity of type III IFNs against RuV infection, especially in the absence of both type I and III IFN signaling, the RuV replication cycle was enhanced. |
| first_indexed | 2024-03-10T03:12:49Z |
| format | Article |
| id | doaj.art-e33f610def564c818cdb222408c04f1f |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T03:12:49Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-e33f610def564c818cdb222408c04f1f2023-11-23T12:32:12ZengMDPI AGPathogens2076-08172022-05-0111553710.3390/pathogens11050537Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus InfectionErik Schilling0Maria Elisabeth Wald1Juliane Schulz2Lina Emilia Werner3Claudia Claus4Institute of Clinical Immunology, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyInstitute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, 04103 Leipzig, GermanyInstitute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyInstitute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyInstitute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyInterferons (IFNs) are an essential part of innate immunity and contribute to adaptive immune responses. Here, we employed a loss-of-function analysis with human A549 respiratory epithelial cells with a knockout (KO) of the type I IFN receptor (IFNAR KO), either solely or together with the receptor of type III IFN (IFNAR/IFNLR1 KO). The course of rubella virus (RuV) infection on the IFNAR KO A549 cells was comparable to the control A549. However, on the IFNAR/IFNLR1 KO A549 cells, both genome replication and the synthesis of viral proteins were significantly enhanced. The generation of IFN β during RuV infection was influenced by type III IFN signaling. In contrast to IFNAR KO A549, extracellular IFN β was not detected on IFNAR/IFNLR1 KO A549. The bioenergetic profile of RuV-infected IFNAR/IFNLR1 KO A549 cells generated by extracellular flux analysis revealed a significant increase in glycolysis, whereas mitochondrial respiration was comparable between all three cell types. Moreover, the application of the glucose analogue 2-deoxy-D-glucose (2-DG) significantly increased viral protein synthesis in control A549 cells, while no effect was noted on IFNAR/IFNLR KO A549. In conclusion, we identified a positive signaling circuit of type III IFN signaling on the generation of IFN β during RuV infection and an IFN signaling-dependent contribution of glycolysis to RuV infection. This study on epithelial A549 cells emphasizes the interaction between glycolysis and antiviral IFN signaling and notably, the antiviral activity of type III IFNs against RuV infection, especially in the absence of both type I and III IFN signaling, the RuV replication cycle was enhanced.https://www.mdpi.com/2076-0817/11/5/537extracellular acidification rateextracellular flux analysisglycolysisoxygen consumption rate2-deoxy-D-glucose |
| spellingShingle | Erik Schilling Maria Elisabeth Wald Juliane Schulz Lina Emilia Werner Claudia Claus Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection Pathogens extracellular acidification rate extracellular flux analysis glycolysis oxygen consumption rate 2-deoxy-D-glucose |
| title | Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection |
| title_full | Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection |
| title_fullStr | Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection |
| title_full_unstemmed | Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection |
| title_short | Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection |
| title_sort | interferon signaling dependent contribution of glycolysis to rubella virus infection |
| topic | extracellular acidification rate extracellular flux analysis glycolysis oxygen consumption rate 2-deoxy-D-glucose |
| url | https://www.mdpi.com/2076-0817/11/5/537 |
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