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Published on: February 28, 2021
Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells
Sneha M Pinto1, Yashwanth Subbannayya1, Hera Kim1
1Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Abstract:
COVID-19 pandemic continues to remain a global health concern owing to the emergence of newer variants. Several multi-Omics studies have produced extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their ensuing effect on the cellular dynamics is critical to expanding the current knowledge on SARS-CoV-2 infections. Through an unbiased transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV-2 Norway/Trondheim-S15 strain induces time-dependent alterations in the induction of type I IFN response, activation of DNA damage response, dysregulated Hippo signaling, among others. We identified interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings serve as a resource of potential targets that can aid in designing novel host-directed therapeutic strategies.
Insights
This study reveals how SARS-CoV-2 infection alters host cell signaling and metabolism using multi-omics. Findings highlight post-translational modifications as key targets for new COVID-19 therapies.
Area of Science:
- Molecular Biology
- Virology
- Systems Biology
Background:
- The COVID-19 pandemic persists due to emerging SARS-CoV-2 variants.
- Understanding host-pathogen interactions, particularly host signaling networks regulated by post-translational modifications, is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the time-dependent molecular and metabolic alterations in human lung cells infected with the SARS-CoV-2 Norway/Trondheim-S15 strain.
- To elucidate the role of post-translational modifications, such as phosphorylation and acetylation, in SARS-CoV-2 pathogenesis.
Main Methods:
- Unbiased multi-omics analysis including transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis.
- Utilized a human lung-derived cell line infected with SARS-CoV-2.
Main Results:
- SARS-CoV-2 infection induced time-dependent changes in type I Interferon (IFN) response, DNA damage response activation, and Hippo signaling dysregulation.
- Identified interplay between phosphorylation and acetylation dynamics on host proteins, affecting metabolite release, notably organic acids and ketone bodies.
Conclusions:
- SARS-CoV-2 infection significantly impacts host cell signaling pathways and metabolic profiles.
- The findings provide a comprehensive resource of potential host-directed therapeutic targets for combating COVID-19.
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