2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation
Abstract Background Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly prolifera...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-023-02082-3 |
| _version_ | 1797811970070544384 |
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| author | Lucia Baďurová Katarína Polčicová Božena Omasta Ingrid Ovečková Eva Kocianová Jana Tomášková |
| author_facet | Lucia Baďurová Katarína Polčicová Božena Omasta Ingrid Ovečková Eva Kocianová Jana Tomášková |
| author_sort | Lucia Baďurová |
| collection | DOAJ |
| description | Abstract Background Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. Methods The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. Results Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. Conclusions Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. |
| first_indexed | 2024-03-13T07:30:39Z |
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| issn | 1743-422X |
| language | English |
| last_indexed | 2024-03-13T07:30:39Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-841d8fea21c442ef96e55dd294cabfbb2023-06-04T11:06:32ZengBMCVirology Journal1743-422X2023-05-0120111810.1186/s12985-023-02082-32-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylationLucia Baďurová0Katarína Polčicová1Božena Omasta2Ingrid Ovečková3Eva Kocianová4Jana Tomášková5Institute of Virology, Biomedical Research Center, Slovak Academy of SciencesInstitute of Virology, Biomedical Research Center, Slovak Academy of SciencesInstitute of Virology, Biomedical Research Center, Slovak Academy of SciencesInstitute of Virology, Biomedical Research Center, Slovak Academy of SciencesInstitute of Virology, Biomedical Research Center, Slovak Academy of SciencesInstitute of Virology, Biomedical Research Center, Slovak Academy of SciencesAbstract Background Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. Methods The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. Results Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. Conclusions Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses.https://doi.org/10.1186/s12985-023-02082-3ArenavirusLCMVCell metabolismGlycolysis2-Deoxy-D-glucoseGlycoprotein |
| spellingShingle | Lucia Baďurová Katarína Polčicová Božena Omasta Ingrid Ovečková Eva Kocianová Jana Tomášková 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation Virology Journal Arenavirus LCMV Cell metabolism Glycolysis 2-Deoxy-D-glucose Glycoprotein |
| title | 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation |
| title_full | 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation |
| title_fullStr | 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation |
| title_full_unstemmed | 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation |
| title_short | 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation |
| title_sort | 2 deoxy d glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein n glycosylation |
| topic | Arenavirus LCMV Cell metabolism Glycolysis 2-Deoxy-D-glucose Glycoprotein |
| url | https://doi.org/10.1186/s12985-023-02082-3 |
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