Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Emerging microbes & infections. Volume 9:Issue 1(2020)
• Page Start: 1748
• Page End: 1760
• Publication Date: 2020-01-01
• Subjects: SARS-CoV-2 -- transcriptomics -- proteomics -- Akt/mTOR/HIF-1 -- MK-2206; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2020.1799723
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: 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.