Open AccessDC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist
Author(s) -
Michel Thépaut,
Joanna Luczkowiak,
Corinne Vivès,
Nuria Labiod,
Isabelle Bally,
Fátima Lasala,
Yasmina Grimoire,
Daphna Fenel,
Sara Sattin,
Nicole M. Thielens,
Guy Schoehn,
Anna Bernardi,
Rafaël Delgado,
Franck Fieschi
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009576
Subject(s) - dc sign , virology , vero cell , biology , glycoprotein , receptor , virus , viral entry , antigen , dendritic cell , immunology , microbiology and biotechnology , viral replication , biochemistry
The efficient spread of SARS-CoV-2 resulted in a unique pandemic 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 (CLR S ) of antigen-presenting cells, widely present in respiratory 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 + Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.