Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry

Several Ebola viruses cause outbreaks of lethal haemorrhagic fever in humans, but developing therapies tackle only Zaire Ebola virus. Dendritic cells (DCs) are targets of this infection in vivo. Here, we found that Ebola virus entry into activated DCs requires the sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169), which recognizes sialylated gangliosides anchored to viral membranes. Blockage of the Siglec-1 receptor by anti-Siglec-1 monoclonal antibodies halted Ebola viral uptake and cytoplasmic entry, offering cross-protection against other ganglioside-containing viruses such as human immunodeficiency virus type 1. The sialic acid-binding Ig-like lectin 1 (Siglec-1, also known as CD169) plays a more prominent role than the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-Grabbing non-integrin in mediating Ebola virus entry into activated dendritic cells, and anti-Siglec-1 monoclonal antibodies can antagonize this process.