90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
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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.
In: CLIN EXP MED, Vol. 23, No. 7, 11.2023, p. 3689-3700.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
AU - Bosquillon de Jarcy, Laure
AU - Akbil, Bengisu
AU - Mhlekude, Baxolele
AU - Leyens, Johanna
AU - Postmus, Dylan
AU - Harnisch, Greta
AU - Jansen, Jenny
AU - Schmidt, Marie L
AU - Aigner, Annette
AU - Pott, Fabian
AU - Chua, Robert Lorenz
AU - Krist, Lilian
AU - Gentile, Roberta
AU - Mühlemann, Barbara
AU - Jones, Terence C
AU - Niemeyer, Daniela
AU - Fricke, Julia
AU - Keil, Thomas
AU - Pischon, Tobias
AU - Janke, Jürgen
AU - Conrad, Christian
AU - Iacobelli, Stefano
AU - Drosten, Christian
AU - Corman, Victor M
AU - Ralser, Markus
AU - Eils, Roland
AU - Kurth, Florian
AU - Sander, Leif
AU - Goffinet, Christine
N1 - © 2023. The Author(s).
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - Humans
KW - Animals
KW - Mice
KW - COVID-19
KW - Caco-2 Cells
KW - HEK293 Cells
KW - Leukocytes, Mononuclear
KW - SARS-CoV-2
KW - Antiviral Agents
KW - RNA, Messenger
KW - Antigens, Neoplasm
KW - Biomarkers, Tumor
U2 - 10.1007/s10238-023-01077-2
DO - 10.1007/s10238-023-01077-2
M3 - SCORING: Journal article
C2 - 37162650
VL - 23
SP - 3689
EP - 3700
JO - CLIN EXP MED
JF - CLIN EXP MED
SN - 1591-8890
IS - 7
ER -