229: Dengue virus infection and induction of proinflammatory cytokines in dendritic cells is profoundly inhibited by selective carbohydrate-binding agents (CBAs)

Abstract

We have demonstrated that several carbohydrate-binding agents (CBAs), such as the plant lectins Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA), have a consistent and serotype-independent anti-dengue virus (DENV) activity in DC-SIGN expressing cells. Because DCs in the skin are the first target cells of this virus we evaluated monocyte-derived dendritic cells (MDDC) generated from human blood. Remarkably, the potency of the CBAs against DENV in MDDC cultures was significantly higher (up to 100-fold) than in Raji/DC-SIGN + cells. The CBAs were also able to completely prevent the DENV-induction of cellular activation and differentiation markers, as measured by flow cytometry. MDDC were also infected with DENV and then the supernatant was analyzed by the Bio-Plex human cytokine 27-plex immunoassay for the production of IFN-γ, IFN-α, RANTES, MIP-1α, MIP-1β and TNF-α, which all have been demonstrated to play a role in the DENV pathogenesis. We observed an enhanced production of all these cytokines/chemokines in the supernatant analyzed 48 h after DENV infection. Addition of 10 μ g/ml of HHA or GNA profoundly inhibited the induction of RANTES, MIP-1α, MIP-1β, IFN-α and TNF-α, and to a lesser extent the production of IFN-γ. The cytokines/chemokines production was also evaluated in uninfected MDDC incubated with CBAs. These agents, by themselves, had no effect on the cytokine/chemokine production profile compared to the uninfected MDDC. Thus, we demonstrated that the CBAs, in addition to their consistent antiviral activity, inhibited the secretion of several pro-inflammatory cytokines and chemokines important in the DENV pathogenesis, rendering CBAs as attractive protein lead structures to combat DENV transmission and infection.