Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
| العنوان: | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
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| المؤلفون: | Appelberg, Sofia, Gupta, Soham, Svensson Akusjärvi, Sara, Ambikan, Anoop T., Mikaeloff, Flora, Saccon, Elisa, Végvári, Ákos, Benfeitas, Rui, Sperk, Maike, Ståhlberg, Marie, Krishnan, Shuba, Singh, Kamal, Penninger, Josef M., Mirazimi, Ali, Neogi, Ujjwal |
| المصدر: | Emerging Microbes & Infections article-version (VoR) Version of Record |
| بيانات النشر: | Taylor & Francis, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Proteomics, Epidemiology, viruses, Immunology, Pneumonia, Viral, Microbiology, Cell Line, transcriptomics, Akt/mTOR/HIF-1, Betacoronavirus, Tandem Mass Spectrometry, Virology, Drug Discovery, Humans, Pandemics, SARS-CoV-2, Gene Expression Profiling, TOR Serine-Threonine Kinases, COVID-19, High-Throughput Nucleotide Sequencing, General Medicine, Articles, Infectious Diseases, MK-2206, Gene Expression Regulation, Parasitology, Hypoxia-Inducible Factor 1, Coronavirus Infections, Proto-Oncogene Proteins c-akt, Research Article, Chromatography, Liquid, Signal Transduction |
| الوصف: | How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients. |
| اللغة: | English |
| تدمد: | 2222-1751 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::c163178144c1dd1027865807d59aaf7cTest http://europepmc.org/articles/PMC7473213Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....c163178144c1dd1027865807d59aaf7c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22221751 |
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