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10.1080/22221751.2020.1799723

http://scihub22266oqcxt.onion/10.1080/22221751.2020.1799723
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32691695!7473213!32691695
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suck abstract from ncbi


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pmid32691695      Emerg+Microbes+Infect 2020 ; 9 (1): 1748-1760
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  • Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells #MMPMID32691695
  • Appelberg S; Gupta S; Svensson Akusjarvi S; Ambikan AT; Mikaeloff F; Saccon E; Vegvari A; Benfeitas R; Sperk M; Stahlberg M; Krishnan S; Singh K; Penninger JM; Mirazimi A; Neogi U
  • Emerg Microbes Infect 2020[Dec]; 9 (1): 1748-1760 PMID32691695show ga
  • 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-1alpha 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.
  • |*Signal Transduction[MESH]
  • |Betacoronavirus/*pathogenicity[MESH]
  • |COVID-19[MESH]
  • |Cell Line[MESH]
  • |Chromatography, Liquid[MESH]
  • |Coronavirus Infections/genetics/metabolism/*virology[MESH]
  • |Gene Expression Profiling/*methods[MESH]
  • |Gene Expression Regulation[MESH]
  • |High-Throughput Nucleotide Sequencing[MESH]
  • |Humans[MESH]
  • |Hypoxia-Inducible Factor 1/genetics/metabolism[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/genetics/metabolism/*virology[MESH]
  • |Proteomics/*methods[MESH]
  • |Proto-Oncogene Proteins c-akt/genetics/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |TOR Serine-Threonine Kinases/genetics/metabolism[MESH]


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