Academic Journal
Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2 induced systemic toxicity
| العنوان: | Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2 induced systemic toxicity |
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| المؤلفون: | Li S, Ma F, Yokota T, Garcia G Jr, Palermo A, Wang Y, Farrell C, Wang YC, Wu R, Zhou Z, Pan C, Morselli M, Teitell MA, Ryazantsev S, Fishbein GA, Ten Hoeve J, Arboleda VA, Bloom J, Dillon BJ, Pellegrini M, Lusis AJ, Graeber TG, Arumugaswami V, Deb A |
| المساهمون: | Li, S, Ma, F, Yokota, T, Garcia, G Jr, Palermo, A, Wang, Y, Farrell, C, Wang, Yc, Wu, R, Zhou, Z, Pan, C, Morselli, M, Teitell, Ma, Ryazantsev, S, Fishbein, Ga, Ten Hoeve, J, Arboleda, Va, Bloom, J, Dillon, Bj, Pellegrini, M, Lusis, Aj, Graeber, Tg, Arumugaswami, V, Deb, A |
| سنة النشر: | 2021 |
| المجموعة: | Università di Parma: CINECA IRIS |
| مصطلحات موضوعية: | Settore MEDS-02/A - Patologia generale, Settore BIOS-08/A - Biologia molecolare, Settore MEDS-10/B - Malattie infettive |
| الوصف: | Extra-pulmonary manifestations of COVID-19 are associated with a much higher mortality rate. Yet, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi-organ involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity and failure to thrive. We demonstrate there is metabolic suppression of oxidative phosphorylation and the tri-carboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia and splenic atrophy mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We perform metabolomic profiling of peripheral blood and identify a panel of TCA cycle metabolites that serve as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, that affects expression of immune response genes and could in part contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2 induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000613769000019; journal:JCI INSIGHT; https://hdl.handle.net/11381/2901237 |
| DOI: | 10.1172/jci.insight.145027 |
| الاتاحة: | https://hdl.handle.net/11381/2901237 https://doi.org/10.1172/jci.insight.145027 |
| رقم الانضمام: | edsbas.B01161F3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1172/jci.insight.145027 |
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