Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is an important binding receptor for dengue virus (DENV) that recognizes N-glycosylation sites on the viral E-glycoprotein. DENV cannot bind nor infect the human B-cell line Raji/0. However, DENV productively infects Raji/DC-SIGN(+) cells that constitutively express DC-SIGN on their surface. IL-4-treated monocytes, expressing high levels of DC-SIGN, are also susceptible for DENV infection. Several carbohydrate-binding agents (CBAs), such as the plant lectins HHA, GNA (mannose-specific) and UDA (N-acetylglucosamine-specific), inhibited dose-dependently the binding of DENV and subsequently viral replication in Raji/DC-SIGN(+) cells (EC(50): 0.1-2.2 microM). These CBAs were clearly more active against DENV in IL-4-treated monocytes (EC(50): 4-56 nM). However, the CBAs were devoid of antiviral activity in DENV-susceptible Vero-B (DC-SIGN(-)) cells, demonstrating cell type-dependent differences in viral entry mechanisms.