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Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
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Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
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Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
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Journal Article
Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
2020
Overview
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.
Publisher
Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
Subject
/ Betacoronavirus - pathogenicity
/ Coronavirus Infections - genetics
/ Coronavirus Infections - metabolism
/ Coronavirus Infections - virology
/ COVID-19
/ Gene Expression Profiling - methods
/ HIF-1
/ High-Throughput Nucleotide Sequencing
/ Humans
/ Hypoxia-Inducible Factor 1 - genetics
/ Hypoxia-Inducible Factor 1 - metabolism
/ MK-2206
/ mTOR
/ Pneumonia, Viral - metabolism
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Severe acute respiratory syndrome coronavirus 2
/ TOR Serine-Threonine Kinases - genetics
