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Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2021; Vol. 20, pp. 100134. Date of Electronic Publication: 2021 Aug 14. - Publication Year :
- 2021
-
Abstract
- Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global health pandemic. COVID-19 severity ranges from an asymptomatic infection to a severe multiorgan disease. Although the inflammatory response has been implicated in the pathogenesis of COVID-19, the exact nature of dysregulation in signaling pathways has not yet been elucidated, underscoring the need for further molecular characterization of SARS-CoV-2 infection in humans. Here, we characterize the host response directly at the point of viral entry through analysis of nasopharyngeal swabs. Multiplexed high-resolution MS-based proteomic analysis of confirmed COVID-19 cases and negative controls identified 7582 proteins and revealed significant upregulation of interferon-mediated antiviral signaling in addition to multiple other proteins that are not encoded by interferon-stimulated genes or well characterized during viral infections. Downregulation of several proteasomal subunits, E3 ubiquitin ligases, and components of protein synthesis machinery was significant upon SARS-CoV-2 infection. Targeted proteomics to measure abundance levels of MX1, ISG15, STAT1, RIG-I, and CXCL10 detected proteomic signatures of interferon-mediated antiviral signaling that differentiated COVID-19-positive from COVID-19-negative cases. Phosphoproteomic analysis revealed increased phosphorylation of several proteins with known antiviral properties as well as several proteins involved in ciliary function (CEP131 and CFAP57) that have not previously been implicated in the context of coronavirus infections. In addition, decreased phosphorylation levels of AKT and PKC, which have been shown to play varying roles in different viral infections, were observed in infected individuals relative to controls. These data provide novel insights that add depth to our understanding of SARS-CoV-2 infection in the upper airway and establish a proteomic signature for this viral infection.<br />Competing Interests: Conflict of interest The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- COVID-19 immunology
COVID-19 virology
Chromatography, Liquid
Epithelial Cells metabolism
Epithelial Cells virology
Humans
Interferons immunology
Interferons metabolism
Phosphoproteins analysis
Phosphoproteins metabolism
Proteasome Endopeptidase Complex metabolism
Protein Kinase C metabolism
Proteome metabolism
Proto-Oncogene Proteins c-akt metabolism
Receptors, Opioid metabolism
Signal Transduction
Tandem Mass Spectrometry
Ubiquitin metabolism
COVID-19 metabolism
Host-Pathogen Interactions physiology
Nasopharynx virology
Proteome analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 20
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 34400346
- Full Text :
- https://doi.org/10.1016/j.mcpro.2021.100134