Human Surfactant Protein A Alleviates SARS-CoV-2 Infectivity in Human Lung Epithelial Cells
Preprint
- 3 April 2023
- preprint
- research article
- Published by Cold Spring Harbor Laboratory
Abstract
SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity. The interactions between human SP-A and SARS-CoV-2 S protein and hACE2 receptor, and SP-A level in COVID-19 patients were assessed by ELISA. The effect of SP-A on SARS-CoV-2 infectivity was analyzed by infecting human lung epithelial cells (A549-ACE2) with pseudoviral particles and infectious SARS-CoV-2 (Delta variant) pre-incubated with SP-A. Virus binding, entry, and infectivity were assessed by RT-qPCR, immunoblotting, and plaque assay. The results showed that human SP-A can bind SARS-CoV-2 S protein/RBD and hACE2 in a dose-dependent manner (p<0.01). Human SP-A inhibited virus binding and entry, and reduce viral load in lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein, and titer (p<0.01). Increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05). Therefore, SP-A plays an important role in mucosal innate immunity against SARS-CoV-2 infectivity by directly binding to the S protein and inhibiting its infectivity in host cells. SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.Keywords
This publication has 40 references indexed in Scilit:
- Antiviral activity of recombinant porcine surfactant protein A against porcine reproductive and respiratory syndrome virus in vitroArchiv für die gesamte Virusforschung, 2016
- Functional analysis of porcine reproductive and respiratory syndrome virus N-glycans in infection of permissive cellsVirology, 2015
- Infection of human alveolar macrophages by human coronavirus strain 229EJournal of General Virology, 2012
- Specific Sites of N-Linked Glycosylation on the Hemagglutinin of H1N1 Subtype Influenza A Virus Determine Sensitivity to Inhibitors of the Innate Immune System and Virulence in MiceThe Journal of Immunology, 2011
- Genetic Complexity of the Human Innate Host Defense Molecules, Surfactant Protein A1 (SP-A1) and SP-A2—Impact on FunctionCritical Reviews™ in Eukaryotic Gene Expression, 2009
- Surfactant Protein A Binds to HIV and Inhibits Direct Infection of CD4+ Cells, but Enhances Dendritic Cell-Mediated Viral TransferThe Journal of Immunology, 2008
- Inhibition of hemagglutination activity of influenza A viruses by SP-A1 and SP-A2 variants expressed in CHO cellsMedical Microbiology and Immunology, 2007
- Pseudomonas aeruginosaprotease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functionsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Surfactant Protein A Binds to the Fusion Glycoprotein of Respiratory Syncytial Virus and Neutralizes Virion InfectivityThe Journal of Infectious Diseases, 1999
- Interactions of Surfactant Protein a with Influenza A Viruses: Binding and NeutralizationThe Journal of Infectious Diseases, 1995