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| Item Type: | Article |
|---|---|
| Title: | 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection |
| Creators Name: | Bosquillon de Jarcy, L. and Akbil, B. and Mhlekude, B. and Leyens, J. and Postmus, D. and Harnisch, G. and Jansen, J. and Schmidt, M.L. and Aigner, A. and Pott, F. and Chua, R.L. and Krist, L. and Gentile, R. and Mühlemann, B. and Jones, T.C. and Niemeyer, D. and Fricke, J. and Keil, T. and Pischon, T. and Janke, J. and Conrad, C. and Iacobelli, S. and Drosten, C. and Corman, V.M. and Ralser, M. and Eils, R. and Kurth, F. and Sander, L. and Goffinet, C. |
| 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. |
| Keywords: | SARS-CoV-2, COVID-19, 90K, LGALS3BP, Interferon, Animals, Mice |
| Source: | Clinical and Experimental Medicine |
| ISSN: | 1591-9528 |
| Publisher: | Springer |
| Volume: | 23 |
| Number: | 7 |
| Page Range: | 3689-3700 |
| Date: | November 2023 |
| Official Publication: | https://doi.org/10.1007/s10238-023-01077-2 |
| PubMed: | View item in PubMed |
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