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Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules.
- Source :
-
Nature immunology [Nat Immunol] 2022 Feb; Vol. 23 (2), pp. 275-286. Date of Electronic Publication: 2022 Jan 31. - Publication Year :
- 2022
-
Abstract
- 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.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Subjects :
- Animals
C-Reactive Protein immunology
C-Reactive Protein metabolism
COVID-19 metabolism
COVID-19 virology
Case-Control Studies
Chlorocebus aethiops
Complement Activation
Coronavirus Nucleocapsid Proteins genetics
Coronavirus Nucleocapsid Proteins immunology
Coronavirus Nucleocapsid Proteins metabolism
Female
Glycosylation
HEK293 Cells
Host-Pathogen Interactions
Humans
Male
Mannose-Binding Lectin genetics
Mannose-Binding Lectin immunology
Mannose-Binding Lectin metabolism
Phosphoproteins genetics
Phosphoproteins immunology
Phosphoproteins metabolism
Polymorphism, Genetic
Protein Binding
Receptors, Pattern Recognition genetics
Receptors, Pattern Recognition metabolism
SARS-CoV-2 genetics
SARS-CoV-2 metabolism
SARS-CoV-2 pathogenicity
Serum Amyloid P-Component immunology
Serum Amyloid P-Component metabolism
Signal Transduction
Spike Glycoprotein, Coronavirus genetics
Spike Glycoprotein, Coronavirus immunology
Spike Glycoprotein, Coronavirus metabolism
Vero Cells
COVID-19 immunology
Immunity, Humoral
Receptors, Pattern Recognition immunology
SARS-CoV-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 35102342
- Full Text :
- https://doi.org/10.1038/s41590-021-01114-w