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

  • 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

Related Research units

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.

Bibliographical data

Original languageEnglish
ISSN1591-8890
DOIs
Publication statusPublished - 11.2023
PubMed 37162650