Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase...

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Published in:Nature immunology Vol. 23; no. 2; pp. 275 - 286
Main Authors: Stravalaci, Matteo, Pagani, Isabel, Paraboschi, Elvezia Maria, Pedotti, Mattia, Doni, Andrea, Scavello, Francesco, Mapelli, Sarah N, Sironi, Marina, Perucchini, Chiara, Varani, Luca, Matkovic, Milos, Cavalli, Andrea, Cesana, Daniela, Gallina, Pierangela, Pedemonte, Nicoletta, Capurro, Valeria, Clementi, Nicola, Mancini, Nicasio, Invernizzi, Pietro, Bayarri-Olmos, Rafael, Garred, Peter, Rappuoli, Rino, Duga, Stefano, Bottazzi, Barbara, Uguccioni, Mariagrazia, Asselta, Rosanna, Vicenzi, Elisa, Mantovani, Alberto, Garlanda, Cecilia
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.02.2022
Subjects:
Animals
Antiviral activity
Antiviral drugs
C-Reactive Protein - immunology
C-Reactive Protein - metabolism
Case-Control Studies
Chlorocebus aethiops
Complement Activation
Coronavirus Nucleocapsid Proteins - genetics
Coronavirus Nucleocapsid Proteins - immunology
Coronavirus Nucleocapsid Proteins - metabolism
Coronaviruses
COVID-19
COVID-19 - immunology
COVID-19 - metabolism
COVID-19 - virology
Female
Gene polymorphism
Glycosylation
HEK293 Cells
Host-Pathogen Interactions
Humans
Humoral immunity
Immunity, Humoral
Innate immunity
Lectins
Male
Mannose
Mannose-binding lectin
Mannose-Binding Lectin - genetics
Mannose-Binding Lectin - immunology
Mannose-Binding Lectin - metabolism
Nucleocapsids
Pattern recognition
Pattern recognition receptors
Pentraxins
Phosphoproteins - genetics
Phosphoproteins - immunology
Phosphoproteins - metabolism
Polymorphism, Genetic
Protein Binding
Proteins
Receptors, Pattern Recognition - genetics
Receptors, Pattern Recognition - immunology
Receptors, Pattern Recognition - metabolism
Respiration
SARS-CoV-2 - genetics
SARS-CoV-2 - immunology
SARS-CoV-2 - metabolism
SARS-CoV-2 - pathogenicity
Serum Amyloid P-Component - immunology
Serum Amyloid P-Component - metabolism
Severe acute respiratory syndrome coronavirus 2
Signal Transduction
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - immunology
Spike Glycoprotein, Coronavirus - metabolism
Spike protein
Vero Cells
ISSN:1529-2908, 1529-2916, 1529-2916
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Summary:The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.
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ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-021-01114-w