Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies

• Published in: Nature (London) Vol. 598; no. 7880; pp. 342 - 347
• Main Authors: Lempp, Florian A., Soriaga, Leah B., Montiel-Ruiz, Martin, Benigni, Fabio, Noack, Julia, Park, Young-Jun, Bianchi, Siro, Walls, Alexandra C., Bowen, John E., Zhou, Jiayi, Kaiser, Hannah, Joshi, Anshu, Agostini, Maria, Meury, Marcel, Dellota, Exequiel, Jaconi, Stefano, Cameroni, Elisabetta, Martinez-Picado, Javier, Vergara-Alert, Júlia, Izquierdo-Useros, Nuria, Virgin, Herbert W., Lanzavecchia, Antonio, Veesler, David, Purcell, Lisa A., Telenti, Amalio, Corti, Davide
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.10.2021; Nature Publishing Group
• Subjects: 101/28; 13/1; 13/109; 13/31; 13/89; 14/19; 14/63; 631/250/2152/2153/1291; 631/250/255/2514; 631/326/596/4130; ACE2; Angiotensin; Angiotensin converting enzyme; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antigens; Binding; Cell adhesion; Cell Adhesion Molecules - metabolism; Cell Fusion; Cell Line; COVID-19; Cricetinae; Datasets; DC-SIGN protein; Dendritic cells; Domains; Female; Health aspects; Humanities and Social Sciences; Humans; Infections; Lectins; Lectins - immunology; Lectins - metabolism; Lectins, C-Type - metabolism; Membrane Fusion; Monoclonal antibodies; multidisciplinary; Neutralization; Neutralizing; Peptidyl-dipeptidase A; Physiological aspects; Receptor mechanisms; Receptors; Receptors, Cell Surface - metabolism; Respiratory tract; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Sialic Acid Binding Ig-like Lectin 1 - metabolism; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Viral infections; United States
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-021-03925-1

SARS-CoV-2 infection—which involves both cell attachment and membrane fusion—relies on the angiotensin-converting enzyme 2 (ACE2) receptor, which is paradoxically found at low levels in the respiratory tract 1 – 3 , suggesting that there may be additional mechanisms facilitating infection. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN and the sialic acid–binding immunoglobulin-like lectin 1 (SIGLEC1) function as attachment receptors by enhancing ACE2-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the amino-terminal domain or to the conserved site at the base of the receptor-binding domain, while poorly neutralizing infection of ACE2-overexpressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the receptor binding motif, while potently neutralizing infection of ACE2-overexpressing cells, poorly neutralize infection of cells expressing DC-SIGN or L-SIGN and trigger fusogenic rearrangement of the spike, promoting cell-to-cell fusion. Collectively, these findings identify a lectin-dependent pathway that enhances ACE2-dependent infection by SARS-CoV-2 and reveal distinct mechanisms of neutralization by different classes of spike-specific antibodies. C-type lectins and SIGLEC1 function as attachment receptors for SARS-CoV-2 and enhance ACE2-mediated infection.