RT Journal Article
SR Electronic
T1 Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.30.070383
DO 10.1101/2020.04.30.070383
A1 Sofia Appelberg
A1 Soham Gupta
A1 Anoop T Ambikan
A1 Flora Mikaeloff
A1 Ákos Végvári
A1 Sara Svensson Akusjärvi
A1 Rui Benfeitas
A1 Maike Sperk
A1 Marie Ståhlberg
A1 Shuba Krishnan
A1 Kamal Singh
A1 Josef M. Penninger
A1 Ali Mirazimi
A1 Ujjwal Neogi
YR 2020
UL http://biorxiv.org/content/early/2020/05/01/2020.04.30.070383.abstract
AB How Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remain 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 significant reduction in activated S6K1 and 4E-BP1 at 72 hours post infection. Unlike other human respiratory viruses, we found a significant inhibition of HIF-1α through the entire time course of the infection, suggesting a crosstalk between the SARS-CoV-2 and the mTOR/HIF-1 signaling. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe COVID-19 patients.Competing Interest StatementThe authors have declared no competing interest.