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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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Number of Authors: 152020 (English)In: Emerging Microbes & Infections, E-ISSN 2222-1751, Vol. 9, no 1, p. 1748-1760Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2020. Vol. 9, no 1, p. 1748-1760
Keywords [en]
SARS-CoV-2, transcriptomics, proteomics, Akt, mTOR, HIF-1, MK-2206
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:su:diva-186196DOI: 10.1080/22221751.2020.1799723ISI: 000558495700001PubMedID: 32691695OAI: oai:DiVA.org:su-186196DiVA, id: diva2:1479856
Available from: 2020-10-27 Created: 2020-10-27 Last updated: 2022-02-25Bibliographically approved

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Gupta, SohamVégvári, ÁkosBenfeitas, Rui

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Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
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