SARS-CoV-2 variants show different host cell proteome profiles with delayed immune response activation in Omicron-infected cells

  • The ancestral SARS-CoV-2 strain that initiated the Covid-19 pandemic at the end of 2019 has rapidly mutated into multiple variants of concern with variable pathogenicity and increasing immune escape strategies. However, differences in host cellular antiviral responses upon infection with SARS-CoV-2 variants remain elusive. Leveraging whole-cell proteomics, we determined host signaling pathways that are differentially modulated upon infection with the clinical isolates of the ancestral SARS-CoV-2 B.1 and the variants of concern Delta and Omicron BA.1. Our findings illustrate alterations in the global host proteome landscape upon infection with SARS-CoV-2 variants and the resulting host immune responses. Additionally, viral proteome kinetics reveal declining levels of viral protein expression during Omicron BA.1 infection when compared to ancestral B.1 and Delta variants, consistent with its reduced replication rates. Moreover, molecular assays reveal deferral activation of specific host antiviral signaling upon Omicron BA.1 and BA.2 infections. Our study provides an overview of host proteome profile of multiple SARS-CoV-2 variants and brings forth a better understanding of the instigation of key immune signaling pathways causative for the differential pathogenicity of SARS-CoV-2 variants.

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Author:Melinda MetzlerORCiD, Rebecca George TharyanORCiDGND, Kevin KlannORCiDGND, Katharina GrikscheitORCiD, Denisa BojkovaORCiDGND, Jindrich CinatlORCiDGND, Georg TascherORCiDGND, Sandra CiesekORCiDGND, Christian MünchORCiD
Parent Title (English):Molecular & cellular proteomics
Place of publication:Amsterdam
Document Type:Article
Date of Publication (online):2023/05/02
Date of first Publication:2023/03/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/11/13
Tag:Covid-19; IRF-3; Interferon; NF-kB; Omicron; Protein-translocation; Proteomics; SARS-CoV-2
Issue:5, art. 100537
Article Number:100537
Page Number:14
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International