دورية أكاديمية
Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication
| العنوان: | Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication |
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| المؤلفون: | Krishnan, Shuba, Nordqvist, Hampus, Ambikan, Anoop T., Gupta, Soham, Sperk, Maike, Svensson-Akusjärvi, Sara, Mikaeloff, Flora, Benfeitas, Rui, Saccon, Elisa, Ponnan, Sivasankaran Munusamy, Rodriguez, Jimmy Esneider, Nikouyan, Negin, Odeh, Amani, Ahlén, Gustaf, Asghar, Muhammad, Sällberg, Matti, Vesterbacka, Jan, Nowak, Piotr, Végvári, Ákos, Sönnerborg, Anders, Treutiger, Carl Johan, Neogi, Ujjwal |
| بيانات النشر: | Umeå universitet, Molekylär Infektionsmedicin, Sverige (MIMS) Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Campus Flemingsberg, Stockholm, Sweden Södersjukhuset, (South General Hospital), Stockholm, Sweden National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden Centre for Infectious Disease Research, Indian Institute of Science (IISc), Karnataka, Bangalore, India Division of Chemistry I, Department of Medical Biochemistry and Biophysics, India Division of Infectious Diseases, Department of Medicine Solna, Sweden Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Campus Flemingsberg, Stockholm, Sweden; Division of Infectious Diseases, Department of Medicine Solna, Sweden Södersjukhuset, (South General Hospital), Stockholm, Sweden; Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Campus Flemingsberg, Stockholm, Sweden; Manipal Institute of Virology (MIV), Manipal Academy of Higher Education, Karnataka, Manipal, India |
| سنة النشر: | 2021 |
| المجموعة: | Umeå University: Publications (DiVA) |
| مصطلحات موضوعية: | Biochemistry and Molecular Biology, Biokemi och molekylärbiologi, Infectious Medicine, Infektionsmedicin |
| الوصف: | Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multiomics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity. We used multiomics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell-line models along with immune phenotyping of metabolite transporters in patient blood cells to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multiomics data to regulate the viral reproduction in vitro. Coronavirus disease 2019 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, glucose transporter 1, in CD8+ T cells, intermediate and nonclassical monocytes, and amino acid transporter, xCT, in classical, intermediate, and nonclassical monocytes. In in vitro lung epithelial cell (Calu-3) infection model, we found that glycolysis and glutaminolysis are essential for virus replication, and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that severe acute respiratory syndrome coronavirus-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Molecular & Cellular Proteomics, 1535-9476, 2021, 20; http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-191306Test; PMID 34619366; ISI:000715949400001; Scopus 2-s2.0-85118437107 |
| DOI: | 10.1016/j.mcpro.2021.100159 |
| الإتاحة: | https://doi.org/10.1016/j.mcpro.2021.100159Test http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-191306Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.60A83A63 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.mcpro.2021.100159 |
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