PT  - JOURNAL ARTICLE
AU  - Florian A. Lempp
AU  - Leah Soriaga
AU  - Martin Montiel-Ruiz
AU  - Fabio Benigni
AU  - Julia Noack
AU  - Young-Jun Park
AU  - Siro Bianchi
AU  - Alexandra C. Walls
AU  - John E. Bowen
AU  - Jiayi Zhou
AU  - Hannah Kaiser
AU  - Maria Agostini
AU  - Marcel Meury
AU  - Exequiel Dellota, Jr.
AU  - Stefano Jaconi
AU  - Elisabetta Cameroni
AU  - Herbert W. Virgin
AU  - Antonio Lanzavecchia
AU  - David Veesler
AU  - Lisa Purcell
AU  - Amalio Telenti
AU  - Davide Corti
TI  - Membrane lectins enhance SARS-CoV-2 infection and influence the neutralizing activity of different classes of antibodies
AID  - 10.1101/2021.04.03.438258
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.03.438258
4099  - http://biorxiv.org/content/early/2021/04/04/2021.04.03.438258.short
4100  - http://biorxiv.org/content/early/2021/04/04/2021.04.03.438258.full
AB  - Investigating the mechanisms of SARS-CoV-2 cellular infection is key to better understand COVID-19 immunity and pathogenesis. Infection, which involves both cell attachment and membrane fusion, relies on the ACE2 receptor that is paradoxically found at low levels in the respiratory tract, suggesting that additional mechanisms facilitating infection may exist. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN and the sialic acid-binding Ig-like lectin 1 (SIGLEC1) function as auxiliary receptors by enhancing ACE2-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the N-terminal domain (NTD) or to the conserved proteoglycan site at the base of the Receptor Binding Domain (RBD), while poorly neutralizing infection of ACE2 over-expressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the Receptor Binding Motif (RBM), while potently neutralizing infection of ACE2 over-expressing 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.Competing Interest StatementF.A.L, L.S., F.B., S.B., M.M-R., J.N., J.Z, H.K., M.A., M.M., E.D., S.J., E.C., H.W.V., A.L., L.P, A.T. and D.C. are employees of Vir Biotechnology and may hold shares in Vir Biotechnology. H.W.V. is a founder of PierianDx and Casma Therapeutics. L.P. is a former employee and shareholder in Regeneron Pharmaceuticals. Neither company provided funding for this work or is performing related work. D.V. is a consultant for Vir Biotechnology Inc. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.