Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
ABSTRACTHow 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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1799723 |
| _version_ | 1797265872059891712 |
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| author | Sofia Appelberg Soham Gupta Sara Svensson Akusjärvi Anoop T. Ambikan Flora Mikaeloff Elisa Saccon Ákos Végvári Rui Benfeitas Maike Sperk Marie Ståhlberg Shuba Krishnan Kamal Singh Josef M. Penninger Ali Mirazimi Ujjwal Neogi |
| author_facet | Sofia Appelberg Soham Gupta Sara Svensson Akusjärvi Anoop T. Ambikan Flora Mikaeloff Elisa Saccon Ákos Végvári Rui Benfeitas Maike Sperk Marie Ståhlberg Shuba Krishnan Kamal Singh Josef M. Penninger Ali Mirazimi Ujjwal Neogi |
| author_sort | Sofia Appelberg |
| collection | DOAJ |
| description | ABSTRACTHow 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. |
| first_indexed | 2024-03-07T17:24:00Z |
| format | Article |
| id | doaj.art-66de1ada232b4d38ac0d4795c2388adb |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-25T00:51:41Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-66de1ada232b4d38ac0d4795c2388adb2024-03-11T16:04:23ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911748176010.1080/22221751.2020.1799723Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cellsSofia Appelberg0Soham Gupta1Sara Svensson Akusjärvi2Anoop T. Ambikan3Flora Mikaeloff4Elisa Saccon5Ákos Végvári6Rui Benfeitas7Maike Sperk8Marie Ståhlberg9Shuba Krishnan10Kamal Singh11Josef M. Penninger12Ali Mirazimi13Ujjwal Neogi14Public Health Agency of Sweden, Solna, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SwedenNational Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, AustriaPublic Health Agency of Sweden, Solna, SwedenDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, SwedenABSTRACTHow 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.https://www.tandfonline.com/doi/10.1080/22221751.2020.1799723SARS-CoV-2transcriptomicsproteomicsAkt/mTOR/HIF-1MK-2206 |
| spellingShingle | Sofia Appelberg Soham Gupta Sara Svensson Akusjärvi Anoop T. Ambikan Flora Mikaeloff Elisa Saccon Ákos Végvári Rui Benfeitas Maike Sperk Marie Ståhlberg Shuba Krishnan Kamal Singh Josef M. Penninger Ali Mirazimi Ujjwal Neogi Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells Emerging Microbes and Infections SARS-CoV-2 transcriptomics proteomics Akt/mTOR/HIF-1 MK-2206 |
| title | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
| title_full | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
| title_fullStr | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
| title_full_unstemmed | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
| title_short | Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells |
| title_sort | dysregulation in akt mtor hif 1 signaling identified by proteo transcriptomics of sars cov 2 infected cells |
| topic | SARS-CoV-2 transcriptomics proteomics Akt/mTOR/HIF-1 MK-2206 |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1799723 |
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