Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies
2021; Nature Portfolio; Volume: 598; Issue: 7880 Linguagem: Inglês
10.1038/s41586-021-03925-1
ISSN1476-4687
AutoresFlorian A. Lempp, Leah Soriaga, Martin Montiel-Ruiz, Fabio Benigni, Julia Noack, Young‐Jun Park, Siro Bianchi, Alexandra C. Walls, John E. Bowen, Jiayi Zhou, Hannah Kaiser, Anshu Joshi, Maria L. Agostini, Marcel Meury, Exequiel Dellota, Stefano Jaconi, Elisabetta Cameroni, Javier Martínez‐Picado, Júlia Vergara‐Alert, Nuria Izquierdo‐Useros, Herbert W. Virgin, Antonio Lanzavecchia, David Veesler, Lisa A. Purcell, Amalio Telenti, Davide Corti,
Tópico(s)Animal Virus Infections Studies
ResumoSARS-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 tract1-3, 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.
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