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90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection

Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its anti...

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Autores principales: Bosquillon de Jarcy, Laure, Akbil, Bengisu, Mhlekude, Baxolele, Leyens, Johanna, Postmus, Dylan, Harnisch, Greta, Jansen, Jenny, Schmidt, Marie L., Aigner, Annette, Pott, Fabian, Chua, Robert Lorenz, Krist, Lilian, Gentile, Roberta, Mühlemann, Barbara, Jones, Terence C., Niemeyer, Daniela, Fricke, Julia, Keil, Thomas, Pischon, Tobias, Janke, Jürgen, Conrad, Christian, Iacobelli, Stefano, Drosten, Christian, Corman, Victor M., Ralser, Markus, Eils, Roland, Kurth, Florian, Sander, Leif, Goffinet, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170455/
https://www.ncbi.nlm.nih.gov/pubmed/37162650
http://dx.doi.org/10.1007/s10238-023-01077-2
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author Bosquillon de Jarcy, Laure
Akbil, Bengisu
Mhlekude, Baxolele
Leyens, Johanna
Postmus, Dylan
Harnisch, Greta
Jansen, Jenny
Schmidt, Marie L.
Aigner, Annette
Pott, Fabian
Chua, Robert Lorenz
Krist, Lilian
Gentile, Roberta
Mühlemann, Barbara
Jones, Terence C.
Niemeyer, Daniela
Fricke, Julia
Keil, Thomas
Pischon, Tobias
Janke, Jürgen
Conrad, Christian
Iacobelli, Stefano
Drosten, Christian
Corman, Victor M.
Ralser, Markus
Eils, Roland
Kurth, Florian
Sander, Leif
Goffinet, Christine
author_facet Bosquillon de Jarcy, Laure
Akbil, Bengisu
Mhlekude, Baxolele
Leyens, Johanna
Postmus, Dylan
Harnisch, Greta
Jansen, Jenny
Schmidt, Marie L.
Aigner, Annette
Pott, Fabian
Chua, Robert Lorenz
Krist, Lilian
Gentile, Roberta
Mühlemann, Barbara
Jones, Terence C.
Niemeyer, Daniela
Fricke, Julia
Keil, Thomas
Pischon, Tobias
Janke, Jürgen
Conrad, Christian
Iacobelli, Stefano
Drosten, Christian
Corman, Victor M.
Ralser, Markus
Eils, Roland
Kurth, Florian
Sander, Leif
Goffinet, Christine
author_sort Bosquillon de Jarcy, Laure
collection PubMed
description Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-023-01077-2.
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spelling pubmed-101704552023-05-11 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection Bosquillon de Jarcy, Laure Akbil, Bengisu Mhlekude, Baxolele Leyens, Johanna Postmus, Dylan Harnisch, Greta Jansen, Jenny Schmidt, Marie L. Aigner, Annette Pott, Fabian Chua, Robert Lorenz Krist, Lilian Gentile, Roberta Mühlemann, Barbara Jones, Terence C. Niemeyer, Daniela Fricke, Julia Keil, Thomas Pischon, Tobias Janke, Jürgen Conrad, Christian Iacobelli, Stefano Drosten, Christian Corman, Victor M. Ralser, Markus Eils, Roland Kurth, Florian Sander, Leif Goffinet, Christine Clin Exp Med Research Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-023-01077-2. Springer International Publishing 2023-05-10 2023 /pmc/articles/PMC10170455/ /pubmed/37162650 http://dx.doi.org/10.1007/s10238-023-01077-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Bosquillon de Jarcy, Laure
Akbil, Bengisu
Mhlekude, Baxolele
Leyens, Johanna
Postmus, Dylan
Harnisch, Greta
Jansen, Jenny
Schmidt, Marie L.
Aigner, Annette
Pott, Fabian
Chua, Robert Lorenz
Krist, Lilian
Gentile, Roberta
Mühlemann, Barbara
Jones, Terence C.
Niemeyer, Daniela
Fricke, Julia
Keil, Thomas
Pischon, Tobias
Janke, Jürgen
Conrad, Christian
Iacobelli, Stefano
Drosten, Christian
Corman, Victor M.
Ralser, Markus
Eils, Roland
Kurth, Florian
Sander, Leif
Goffinet, Christine
90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title_full 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title_fullStr 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title_full_unstemmed 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title_short 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
title_sort 90k/lgals3bp expression is upregulated in covid-19 but may not restrict sars-cov-2 infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170455/
https://www.ncbi.nlm.nih.gov/pubmed/37162650
http://dx.doi.org/10.1007/s10238-023-01077-2
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