RT Journal Article
SR Electronic
T1 DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.09.242917
DO 10.1101/2020.08.09.242917
A1 Thépaut, Michel
A1 Luczkowiak, Joanna
A1 Vivès, Corinne
A1 Labiod, Nuria
A1 Bally, Isabelle
A1 Lasala, Fátima
A1 Grimoire, Yasmina
A1 Fenel, Daphna
A1 Sattin, Sara
A1 Thielens, Nicole
A1 Schoehn, Guy
A1 Bernardi, Anna
A1 Delgado, Rafael
A1 Fieschi, Franck
YR 2020
UL http://biorxiv.org/content/early/2020/08/10/2020.08.09.242917.abstract
AB The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesisCompeting Interest StatementThe authors have declared no competing interest.