Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies
Por:
Lempp, FA, Soriaga, LB, Montiel-Ruiz, M, Benigni, F, Noack, J, Park, YJ, Bianchi, S, Walls, AC, Bowen, JE, Zhou, JY, Kaiser, H, Joshi, A, Agostini, M, Meury, M, Dellota, E, Jaconi, S, Cameroni, E, Martinez-Picado, J, Vergara-Alert, J, Izquierdo-Useros, N, Virgin, HW, Lanzavecchia, A, Veesler, D, Purcell, LA, Telenti, A and Corti, D
Publicada:
14 oct 2021
Ahead of Print:
1 ago 2021
Resumen:
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.
Filiaciones:
Lempp, FA:
Vir Biotechnol, San Francisco, CA 94158 USA
Soriaga, LB:
Vir Biotechnol, San Francisco, CA 94158 USA
Montiel-Ruiz, M:
Vir Biotechnol, San Francisco, CA 94158 USA
Benigni, F:
Humabs Biomed SA, Bellinzona, Switzerland
Noack, J:
Vir Biotechnol, San Francisco, CA 94158 USA
Park, YJ:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Bianchi, S:
Humabs Biomed SA, Bellinzona, Switzerland
Walls, AC:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Bowen, JE:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Zhou, JY:
Vir Biotechnol, San Francisco, CA 94158 USA
Kaiser, H:
Vir Biotechnol, San Francisco, CA 94158 USA
Joshi, A:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Agostini, M:
Vir Biotechnol, San Francisco, CA 94158 USA
Meury, M:
Vir Biotechnol, San Francisco, CA 94158 USA
Dellota, E:
Vir Biotechnol, San Francisco, CA 94158 USA
Jaconi, S:
Humabs Biomed SA, Bellinzona, Switzerland
Cameroni, E:
Humabs Biomed SA, Bellinzona, Switzerland
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Vergara-Alert, J:
IRTA UAB, IRTA, Ctr Recerca Sanitat Anim CReSA, Campus UAB, Bellaterra, Cerdanyola Del, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
Virgin, HW:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
UT Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA
Lanzavecchia, A:
Humabs Biomed SA, Bellinzona, Switzerland
Veesler, D:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Purcell, LA:
Vir Biotechnol, St Louis, MO USA
Telenti, A:
Vir Biotechnol, San Francisco, CA 94158 USA
Corti, D:
Vir Biotechnol, San Francisco, CA 94158 USA
Bronze
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