1. 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection
- Author
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Laure Bosquillon de Jarcy, Bengisu Akbil, Baxolele Mhlekude, Johanna Leyens, Dylan Postmus, Greta Harnisch, Jenny Jansen, Marie L. Schmidt, Annette Aigner, Fabian Pott, Robert Lorenz Chua, Lilian Krist, Roberta Gentile, Barbara Mühlemann, Terence C. Jones, Daniela Niemeyer, Julia Fricke, Thomas Keil, Tobias Pischon, Jürgen Janke, Christian Conrad, Stefano Iacobelli, Christian Drosten, Victor M. Corman, Markus Ralser, Roland Eils, Florian Kurth, Leif Sander, and Christine Goffinet
- Subjects
Cardiovascular and Metabolic Diseases ,General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
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.
- Published
- 2023