Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells

Sneha M Pinto; Yashwanth Subbannayya; Hera Kim; Lars Hagen; Maria W Górna; Anni I Nieminen; Magnar Bjørås; Terje Espevik; Denis Kainov; Richard K Kandasamy

doi:10.1016/j.isci.2022.105895

Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells

iScience. 2023 Jan 20;26(1):105895. doi: 10.1016/j.isci.2022.105895. Epub 2022 Dec 28.

Authors

Sneha M Pinto¹, Yashwanth Subbannayya¹, Hera Kim¹, Lars Hagen^{2

3}, Maria W Górna⁴, Anni I Nieminen⁵, Magnar Bjørås², Terje Espevik¹, Denis Kainov², Richard K Kandasamy^{1

2

6}

Affiliations

¹ Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway.
² Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
³ Proteomics and Modomics Experimental Core, PROMEC, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
⁴ Structural Biology Group, Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Warsaw, Poland.
⁵ Institute for Molecular Medicine Finland, University of Helsinki, 00014Helsinki, Finland.
⁶ Department of Laboratory Medicine and Pathology, Centre for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.

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.

Keywords: Metabolomics; Proteomics; Transcriptomics; Virology.