DC-SIGN and Galectin-3 individually and collaboratively regulate H5N1 and H7N9 avian influenza A virus infection via interaction with viral envelope hemagglutinin protein.

This article investigates the individual and combined roles of two lectins, dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) and Galectin-3 (Gal3), in regulating infections by H5N1 and H7N9 avian influenza viruses (AIVs), which are significant global health threats according to the World Health Organization. Using human lung A549 cells engineered to express DC-SIGN or with Gal3 knockdown, the study demonstrates that DC-SIGN expression enhances, while Gal3 knockdown reduces, viral infection by both H5N1 and H7N9 reverse-genetics viruses. Furthermore, co-expression of DC-SIGN and Gal3 synergistically increases viral infectivity, primarily through direct interactions with the highly glycosylated hemagglutinin (HA) protein of these viruses. The findings suggest that targeting the interactions between HA and these lectins could provide alternative antiviral strategies against H5N1 and H7N9 AIV infections.