Journal
NATURE
Volume 598, Issue 7880, Pages 342-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03925-1
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Funding
- Grifols
- Spanish Ministry of Science and Innovation [PID2020-117145RB-I00, PID2019-109870RB-I00]
- National Institute of Allergy and Infectious Diseases [DP1AI158186, HHSN272201700059C]
- Pew Biomedical Scholars Award
- Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund
- Fast Grants
- Yomecorono
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The study reveals that C-type lectin receptors and other factors can serve as attachment receptors for SARS-CoV-2 infection, enhancing ACE2-mediated infection and modulating the neutralizing activity of antibodies.
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.
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