Cargando…

Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx

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 i...

Descripción completa

Detalles Bibliográficos
Autores principales: Vanderboom, Patrick M., Mun, Dong-Gi, Madugundu, Anil K., Mangalaparthi, Kiran K., Saraswat, Mayank, Garapati, Kishore, Chakraborty, Rana, Ebihara, Hideki, Sun, Jie, Pandey, Akhilesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363427/
https://www.ncbi.nlm.nih.gov/pubmed/34400346
http://dx.doi.org/10.1016/j.mcpro.2021.100134
_version_ 1783738350589444096
author Vanderboom, Patrick M.
Mun, Dong-Gi
Madugundu, Anil K.
Mangalaparthi, Kiran K.
Saraswat, Mayank
Garapati, Kishore
Chakraborty, Rana
Ebihara, Hideki
Sun, Jie
Pandey, Akhilesh
author_facet Vanderboom, Patrick M.
Mun, Dong-Gi
Madugundu, Anil K.
Mangalaparthi, Kiran K.
Saraswat, Mayank
Garapati, Kishore
Chakraborty, Rana
Ebihara, Hideki
Sun, Jie
Pandey, Akhilesh
author_sort Vanderboom, Patrick M.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8363427
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-83634272021-08-15 Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx Vanderboom, Patrick M. Mun, Dong-Gi Madugundu, Anil K. Mangalaparthi, Kiran K. Saraswat, Mayank Garapati, Kishore Chakraborty, Rana Ebihara, Hideki Sun, Jie Pandey, Akhilesh Mol Cell Proteomics Research 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. American Society for Biochemistry and Molecular Biology 2021-08-14 /pmc/articles/PMC8363427/ /pubmed/34400346 http://dx.doi.org/10.1016/j.mcpro.2021.100134 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research
Vanderboom, Patrick M.
Mun, Dong-Gi
Madugundu, Anil K.
Mangalaparthi, Kiran K.
Saraswat, Mayank
Garapati, Kishore
Chakraborty, Rana
Ebihara, Hideki
Sun, Jie
Pandey, Akhilesh
Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title_full Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title_fullStr Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title_full_unstemmed Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title_short Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx
title_sort proteomic signature of host response to sars-cov-2 infection in the nasopharynx
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363427/
https://www.ncbi.nlm.nih.gov/pubmed/34400346
http://dx.doi.org/10.1016/j.mcpro.2021.100134
work_keys_str_mv AT vanderboompatrickm proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT mundonggi proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT madugunduanilk proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT mangalaparthikirank proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT saraswatmayank proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT garapatikishore proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT chakrabortyrana proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT ebiharahideki proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT sunjie proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx
AT pandeyakhilesh proteomicsignatureofhostresponsetosarscov2infectioninthenasopharynx