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Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
- Appelberg, Sofia (author)
-
- Gupta, Soham (author)
- Karolinska Institutet
-
- Svensson Akusjärvi, Sara (author)
- Karolinska Institutet
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- Ståhlberg, Marie (author)
- Krishnan, Shuba (author)
- Singh, Kamal (author)
- Penninger, Josef M. (author)
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- (creator_code:org_t)
- 2020-07-31
- 2020
- English.
- In: Emerging Microbes & Infections. - : Informa UK Limited. - 2222-1751. ; 9:1, s. 1748-1760
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- SARS-CoV-2
- transcriptomics
- proteomics
- Akt
- mTOR
- HIF-1
- MK-2206
Publication and Content Type
- ref (subject category)
- art (subject category)
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