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
Affiliations
Sneha M. Pinto
Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway; Corresponding author
Yashwanth Subbannayya
Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Hera Kim
Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Lars Hagen
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Proteomics and Modomics Experimental Core, PROMEC, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Maria W. Górna
Structural Biology Group, Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Warsaw, Poland
Anni I. Nieminen
Institute for Molecular Medicine Finland, University of Helsinki, 00014Helsinki, Finland
Magnar Bjørås
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Terje Espevik
Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Denis Kainov
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Richard K. Kandasamy
Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Department of Laboratory Medicine and Pathology, Centre for Individualized Medicine, Mayo Clinic, Rochester, MN, USA; Corresponding author
Summary: 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.
