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

Published version
Peer-reviewed

Repository DOI


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Authors

Bosquillon de Jarcy, Laure 
Akbil, Bengisu 
Mhlekude, Baxolele 
Leyens, Johanna 
Postmus, Dylan 

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.

Description

Acknowledgements: B.A. and F.P. are supported by the Charité PhD programme. We thank all participants who took part in NAKO and the staff in this research program.


Funder: Berlin Institute of Health; doi: http://dx.doi.org/10.13039/501100017268


Funder: Charité - Universitätsmedizin Berlin (3093)

Keywords

90K, COVID-19, Interferon, LGALS3BP, SARS-CoV-2, Humans, Animals, Mice, COVID-19, Caco-2 Cells, HEK293 Cells, Leukocytes, Mononuclear, SARS-CoV-2, Antiviral Agents, RNA, Messenger, Antigens, Neoplasm, Biomarkers, Tumor

Journal Title

Clin Exp Med

Conference Name

Journal ISSN

1591-8890
1591-9528

Volume Title

23

Publisher

Springer Science and Business Media LLC
Sponsorship
NIAID-NIH CEIRS (HHSN272201400008C)
Bundesministerium für Bildung und Forschung (01ER1301A/B/C)
Deutsche Forschungsgemeinschaft (158989968)