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.
【저자키워드】 SARS-CoV-2, proteomics, transcriptomics, Akt/mTOR/HIF-1, MK-2206, 【초록키워드】 COVID-19, Innate immunity, Infection, inhibition, in vitro, virus, management, pathway, molecular, inhibitor, signaling pathways, patients, cellular response, Coronavirus-2, cellular, Analysis, Pathways, acute respiratory syndrome, severe coronavirus disease, HIF-1α, ErbB, HIF-1, infected cell, potential therapy, downstream, post infection, virus production, mTOR signaling, Host, TNF signaling, Course, performed, required, reduction in, hpi, effector molecule, engage, modulated, 24 hour, dose-dependent activation, Huh7 cell, S6K1, the SARS-CoV-2, 【제목키워드】 Signaling, SARS-CoV-2 infected cell,