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

Appelberg, Sofia; Gupta, Soham; Akusjärvi, Sara Svensson; Ambikan, Anoop T.; Mikaeloff, Flora; Saccon, Elisa; Végvári, Ákos; Benfeitas, Rui; Sperk, Maike; Ståhlberg, Marie; Krishnan, Shuba; Singh, Kamal; Penninger, Josef; Mirazimi, Alì; Neogi, Ujjwal

doi:10.1080/22221751.2020.1799723

Cited by 244 publications

(308 citation statements)

References 46 publications

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“…Recently, Appelberg et al conducted an integrative proteo-transcriptomics analysis of Huh7 cells responding to SARS-CoV-2 infection, and identified ErbB, HIF-1, mTOR, and TNF signaling pathways that were significantly regulated during SARS-CoV-2 infection in vitro. 78 They further demonstrated that the Akt inhibitor MK-2206, targeting the mTOR signaling pathway, was able to significantly reduce the replication of SARS-CoV-2. Moreover, another recent study investigated the translatome and proteome of Caco-2 cells in response to SARS-CoV-2 infection in vitro, and discovered that several cellular pathways linked to translation, proteostasis, splicing, carbon metabolism, and nucleotide metabolism were reshaped during viral infection.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS

Zhou

et al. 2020

J. Proteome Res.

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Porcine deltacoronavirus (PDCoV) is an emergent enteropathogenic coronavirus associated with swine diarrhea. Porcine small intestinal epithelial cells (IPEC) are the primary target cells of PDCoV infection in vivo. Here, isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled to liquid chromatography–tandem mass spectrometry (LC-MS/MS) was used to quantitatively identify differentially expressed proteins (DEPs) in PDCoV-infected IPEC-J2 cells. A total of 78 DEPs, including 23 upregulated and 55 downregulated proteins, were identified at 24 h postinfection. The data are available via ProteomeXchange with identifier PXD019975. To ensure reliability of the proteomics data, two randomly selected DEPs, the downregulated anaphase-promoting complex subunit 7 (ANAPC7) and upregulated interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), were verified by real-time PCR and Western blot, and the results of which indicate that the proteomics data were reliable and valid. Bioinformatics analyses, including GO, COG, KEGG, and STRING, further demonstrated that a majority of the DEPs are involved in numerous crucial biological processes and signaling pathways, such as immune system, digestive system, signal transduction, RIG-I-like receptor, mTOR, PI3K-AKT, autophagy, and cell cycle signaling pathways. Altogether, this is the first study on proteomes of PDCoV-infected host cells, which shall provide valuable clues for further investigation of PDCoV pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS

Zhou

et al. 2020

J. Proteome Res.

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“…The proteins were hereby quantified with TMT labeling and reversed-phase liquid chromatography tandem mass spectrometry (RPLC-MS/MS). 62 In another proteomics study with SARS-CoV-2, which also utilized TMT-based quantification, Caco-2 cells (human colorectal tumor cell line) were infected and studied over time. Cellular pathways, such as cholesterol metabolism, translation, splicing, and carbon metabolism, were identified to be reshaped during viral infection.…”

Section: Coronavirusesmentioning

confidence: 99%

Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses

et al. 2020

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Emerging and re-emerging infectious diseases due to RNA viruses cause major negative consequences for the quality of life, public health, and overall economic development. Most of the RNA viruses causing illnesses in humans are of zoonotic origin. Zoonotic viruses can directly be transferred from animals to humans through adaptation, followed by human-to-human transmission, such as in human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and, more recently, SARS coronavirus 2 (SARS-CoV-2), or they can be transferred through insects or vectors, as in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), Zika virus (ZIKV), and dengue virus (DENV). At the present, there are no vaccines or antiviral compounds against most of these viruses. Because proteins possess a vast array of functions in all known biological systems, proteomics-based strategies can provide important insights into the investigation of disease pathogenesis and the identification of promising antiviral drug targets during an epidemic or pandemic. Mass spectrometry technology has provided the capacity required for the precise identification and the sensitive and high-throughput analysis of proteins on a large scale and has contributed greatly to unravelling key protein–protein interactions, discovering signaling networks, and understanding disease mechanisms. In this Review, we present an account of quantitative proteomics and its application in some prominent recent examples of emerging and re-emerging RNA virus diseases like HIV-1, CCHFV, ZIKV, and DENV, with more detail with respect to coronaviruses (MERS-CoV and SARS-CoV) as well as the recent SARS-CoV-2 pandemic.

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“…Virus production was significantly reduced by the inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206. Further, the authors suggested profound studies are required for the treatment of COVID-19 patients (Appelberg et al 2020 ).…”

Section: Proteomics For Sarsmentioning

confidence: 99%

A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies

2020

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World Health Organisation declared COVID-19 a pandemic on March 11, 2020. It was temporarily named as 2019-nCoV then subsequently named as COVID-19 virus. A coronavirus is a group of viruses, known to be zoonotic, causing illness ranging from acute to mild respiratory infections. These are spherical or pleomorphic enveloped particles containing positive sense RNA. The virus enters host cells, its uncoated genetic material transcribes, and translates. Since it has started spreading rapidly, protective measures have been taken all over the world. However, its transmission has been proved to be unstoppable and the absence of an effective drug makes the situation worse. The scientific community has gone all-out to discover and develop a possible vaccine or a competent antiviral drug. Other domains of biological sciences that promise effective results and target somewhat stable entities that are proteins, could be very useful in this time of crisis. Proteomics and metabolomics are the vast fields that are equipped with sufficient technologies to face this challenge. Various protein separation and identification techniques are available which facilitates the analysis of various types of interactions among proteins and their evolutionary lineages. The presented review aims at confronting the question: ‘how proteomics can help in tackling SARS-CoV-2?’ It deals with the role of upcoming proteome technology in these pandemic situations and discusses the proteomics approach towards the COVID-19 dilemma.

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

Cited by 244 publications

References 46 publications

Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS

Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS

Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses

A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies

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