Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon

Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. Howe...

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Autores principales: Jordi Mayneris-Perxachs, José Maria Moreno-Navarrete, Marta Ballanti, Giovanni Monteleone, Omero Alessandro Paoluzi, Geltrude Mingrone, Philippe Lefebvre, Bart Staels, Massimo Federici, Josep Puig, Josep Garre, Rafael Ramos, José-Manuel Fernández-Real
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/e6d9828765e5476d93963cd04887d8c5
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spelling oai:doaj.org-article:e6d9828765e5476d93963cd04887d8c52021-11-20T05:05:24ZLipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon2001-037010.1016/j.csbj.2021.11.007https://doaj.org/article/e6d9828765e5476d93963cd04887d8c52021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2001037021004724https://doaj.org/toc/2001-0370Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.Jordi Mayneris-PerxachsJosé Maria Moreno-NavarreteMarta BallantiGiovanni MonteleoneOmero Alessandro PaoluziGeltrude MingronePhilippe LefebvreBart StaelsMassimo FedericiJosep PuigJosep GarreRafael RamosJosé-Manuel Fernández-RealElsevierarticleLipidomicsMetabolomicsOmega-3 fatty acidsSARS-CoV-2Viral receptorsBiotechnologyTP248.13-248.65ENComputational and Structural Biotechnology Journal, Vol 19, Iss , Pp 6080-6089 (2021)
institution DOAJ
collection DOAJ
language EN
topic Lipidomics
Metabolomics
Omega-3 fatty acids
SARS-CoV-2
Viral receptors
Biotechnology
TP248.13-248.65
spellingShingle Lipidomics
Metabolomics
Omega-3 fatty acids
SARS-CoV-2
Viral receptors
Biotechnology
TP248.13-248.65
Jordi Mayneris-Perxachs
José Maria Moreno-Navarrete
Marta Ballanti
Giovanni Monteleone
Omero Alessandro Paoluzi
Geltrude Mingrone
Philippe Lefebvre
Bart Staels
Massimo Federici
Josep Puig
Josep Garre
Rafael Ramos
José-Manuel Fernández-Real
Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
description Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.
format article
author Jordi Mayneris-Perxachs
José Maria Moreno-Navarrete
Marta Ballanti
Giovanni Monteleone
Omero Alessandro Paoluzi
Geltrude Mingrone
Philippe Lefebvre
Bart Staels
Massimo Federici
Josep Puig
Josep Garre
Rafael Ramos
José-Manuel Fernández-Real
author_facet Jordi Mayneris-Perxachs
José Maria Moreno-Navarrete
Marta Ballanti
Giovanni Monteleone
Omero Alessandro Paoluzi
Geltrude Mingrone
Philippe Lefebvre
Bart Staels
Massimo Federici
Josep Puig
Josep Garre
Rafael Ramos
José-Manuel Fernández-Real
author_sort Jordi Mayneris-Perxachs
title Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
title_short Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
title_full Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
title_fullStr Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
title_full_unstemmed Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
title_sort lipidomics and metabolomics signatures of sars-cov-2 mediators/receptors in peripheral leukocytes, jejunum and colon
publisher Elsevier
publishDate 2021
url https://doaj.org/article/e6d9828765e5476d93963cd04887d8c5
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