s10238-023-01077-2.pdf (1.48 MB)
90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection.
journal contributionposted on 2023-11-09, 13:45 authored by 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, Christine Goffinet
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.
Crick (Grant ID: 10134, Grant title: Ralser FC001134)