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Received for publication August 25, 2006.
Revised October 4, 2006.
Accepted for publication October 20, 2006.
Exposure of HIV-1 to DC-SIGN-expressing B-lymphoblast Raji cells (Raji/DC-SIGN) but not to wild-type Raji/0 cells results in the capture of HIV-1 particles to the cells as measured by the quantification of cell-associated p24 antigen. Co-cultivation of HIV-1-captured Raji/DC-SIGN cells with uninfected CD4+ T-lymphocyte C8166 cells results in abundant formation of syncytia within 36 hrs post co-cultivation. Short pre-exposure of HIV-1 to carbohydrate-binding agents (CBA) dose-dependently prevents the Raji/DC-SIGN cells to efficiently bind the virus particles and no syncytia formation occurs upon subsequent co-cultivation with C8166 cells. Thus, the mannose-specific (i.e. the plant lectins HHA, GNA, NPA and CA, the procaryotic cyanovirin-N (CV-N) and the monoclonal antibody 2G12)- and GlcNAc-specific (i.e. the plant lectin UDA) CBAs efficiently abrogate the DC-SIGN-directed HIV-1 capture and subsequent transmission to T-lymphocytes. In this assay, the CD4-down regulating CADA derivative, the CXCR4 and CCR5 co-receptor antagonists AMD3100 and Maraviroc, the gp41-binding enfuvirtide and the polyanionic substances DS-5000, PVAS and PRO-2000 were markedly less efficient or even ineffective at all. Similar observations were made in primary monocyte-derived dendritic cell cultures that were infected with HIV-1 particles that had been shortly pre-exposed to the CBAs CV-N, CA, HHA and GNA, and the polyanions DS-5000 and PRO-2000. The potential of CBAs, but not polyanions and other structural/functional classes of entry inhibitors to impair DC-SIGN-expressing cells in their capacity of transmitting HIV to T-lymphocytes might be an important property to be taken into consideration in the eventual choice to move microbicide candidate drugs to the clinical setting.
Key words:
Protein targets, Antiviral drugs
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