WP5 - Biological Studies


WP5 will provide selected experiments to test the biological activity of the most promising compounds developed in this network. Initially, these studies will analyze the biological effects produced by the interaction of these synthetic compounds and DC-SIGN (viral entry, internalization processes, activation of immunological pathways, intracellular signalling, etc.).

a. The Amsterdam group is responsible for synthesizing ligands to inhibit pathogen (HIV-1, Measles, Schistosomes), binding to DC and DC-SIGN, and will analyze viral entry and transmission processes of HIV when DC are targeted by these glycan inhibitors. Furthermore it will be assessed whether the components affect DC adhesion and maturation, cytokine production profile, and antigen presentation of DC. We will screen various human mucosal tissues and skin to determine binding activity and co-localization with DC-SIGN.

b. The Laboratory of Molecular Microbiology at Madrid will produce recombinant viruses expressing a wide variety of envelope glycoproteins from different viral agents and will contribute, showing the different stages of HIV infection: primary and acute infection, chronic infection, subtypes A, B, C, D, G and recombinant circulating forms. LMM also will be in charge of conducting a joint of experiments of infection with cell lines and primary cells dendritic cell and different subsets of lymphocytes from human blood.

c. The INSERM team will focus on the identification of carbohydrate compounds and conjugates that block Flaviridae (HCV, Dengue virus, West Nile virus) interactions with DC- and L-SIGN. For this aim, soluble envelope glycoproteins and infectious viral particles will be generated. Biochemical studies to identify the multivalent systems that block soluble glycoprotein binding to DC- and L-SIGN expressing cells will be performed. Inhibitors will be then tested for their capacity to prevent DC infection as well virus transmission to target cells.