Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies
© 2021. The Author(s), under exclusive licence to Springer Nature Limited..
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 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:598 |
|---|---|
| Enthalten in: |
Nature - 598(2021), 7880 vom: 16. Okt., Seite 342-347 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lempp, Florian A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.10.2021 Date Revised 27.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41586-021-03925-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM330076515 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM330076515 | ||
| 003 | DE-627 | ||
| 005 | 20231225210521.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41586-021-03925-1 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1100.xml |
| 035 | |a (DE-627)NLM330076515 | ||
| 035 | |a (NLM)34464958 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lempp, Florian A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.10.2021 | ||
| 500 | |a Date Revised 27.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s), under exclusive licence to Springer Nature Limited. | ||
| 520 | |a 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 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a CLEC4M protein, human |2 NLM | |
| 650 | 7 | |a Cell Adhesion Molecules |2 NLM | |
| 650 | 7 | |a DC-specific ICAM-3 grabbing nonintegrin |2 NLM | |
| 650 | 7 | |a Lectins |2 NLM | |
| 650 | 7 | |a Lectins, C-Type |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a SIGLEC1 protein, human |2 NLM | |
| 650 | 7 | |a Sialic Acid Binding Ig-like Lectin 1 |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Soriaga, Leah B |e verfasserin |4 aut | |
| 700 | 1 | |a Montiel-Ruiz, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Benigni, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a Noack, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Young-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Bianchi, Siro |e verfasserin |4 aut | |
| 700 | 1 | |a Walls, Alexandra C |e verfasserin |4 aut | |
| 700 | 1 | |a Bowen, John E |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Kaiser, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Joshi, Anshu |e verfasserin |4 aut | |
| 700 | 1 | |a Agostini, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Meury, Marcel |e verfasserin |4 aut | |
| 700 | 1 | |a Dellota, Exequiel |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Jaconi, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Cameroni, Elisabetta |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez-Picado, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Vergara-Alert, Júlia |e verfasserin |4 aut | |
| 700 | 1 | |a Izquierdo-Useros, Nuria |e verfasserin |4 aut | |
| 700 | 1 | |a Virgin, Herbert W |e verfasserin |4 aut | |
| 700 | 1 | |a Lanzavecchia, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Veesler, David |e verfasserin |4 aut | |
| 700 | 1 | |a Purcell, Lisa A |e verfasserin |4 aut | |
| 700 | 1 | |a Telenti, Amalio |e verfasserin |4 aut | |
| 700 | 1 | |a Corti, Davide |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature |d 1945 |g 598(2021), 7880 vom: 16. Okt., Seite 342-347 |w (DE-627)NLM000008257 |x 1476-4687 |7 nnns |
| 773 | 1 | 8 | |g volume:598 |g year:2021 |g number:7880 |g day:16 |g month:10 |g pages:342-347 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41586-021-03925-1 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 598 |j 2021 |e 7880 |b 16 |c 10 |h 342-347 | ||