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bioRxiv · 10.1101/2020.04.30.070383

Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Appelberg, S.·Gupta, S.·Ambikan, A. T.·Mikaeloff, F.·Vegvari, A.·Svensson Akusjarvi, S.·Benfeitas, R.·Sperk, M.·Stahlberg, M.·Krishnan, S.·Singh, K.·Penninger, J. M.·Mirazimi, A.·Neogi, U.
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Abstract

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-1 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.

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Appelberg, S., Gupta, S., Ambikan, A. T., Mikaeloff, F., Vegvari, A., Svensson Akusjarvi, S., Benfeitas, R., Sperk, M., Stahlberg, M., Krishnan, S., Singh, K., Penninger, J. M., Mirazimi, A., Neogi, U.. 2020-05-01. Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells. https://doi.org/10.1101/2020.04.30.070383

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