Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses.
Dengue virus (DV) is a mosquito-borne flavivirus that causes haemorrhagic fever in humans. DV primarily targets immature dendritic cells (DCs) after a bite by an infected mosquito vector. Here, we analysed the interactions between DV and human-monocyte-derived DCs at the level of virus entry. We show that the DC-specific ICAM3-grabbing non-integrin (DC-SIGN) molecule, a cell-surface, mannose-specific, C-type lectin, binds mosquito-cell-derived DVs and allows viral replication. Conclusive evidence for the involvement of DC-SIGN in DV infection was obtained by the inhibition of viral infection by anti-DC-SIGN antibodies and by the soluble tetrameric ectodomain of DC-SIGN. Our data show that DC-SIGN functions as a DV-binding lectin by interacting with the DV envelope glycoprotein. Mosquito-cell-derived DVs may have differential infectivity for DC-SIGN-expressing cells. We suggest that the differential use of DC-SIGN by viral envelope glycoproteins may account for the immunopathogenesis of DVs.
Navarro-Sanchez
Erika
E
Interactions Moléculaires Flavivirus-Hôtes, 25 Rue du Dr Roux, 75724 Paris, France.
Altmeyer
Ralf
R
Amara
Ali
A
Schwartz
Olivier
O
Fieschi
Franck
F
Virelizier
Jean-Louis
JL
Arenzana-Seisdedos
Fernando
F
Desprès
Philippe
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D009033:Culicidae / Q000821:virology*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C483616:ICAM3 protein, human