Background:  HIV entry inhibitors may represent good candidate compounds as microbicide drugs because they have the potential to inhibit both virus infection of susceptible cells and syncytia formation between (persistently) infected cells and uninfected lymphocytes. It would be important to reveal whether the compounds also prevent DC-SIGN-directed capture of HIV particles and subsequent viral transmission to CD4⁺ T lymphocytes.

Methods:  HIV-1(III_B) particles were pre-exposed to carbohydrate-binding agents (CBA) and polyanions for 30 minutes prior to addition of Raji/DC-SIGN cells for 60 minutes. Then, the cells were carefully washed and cell-associated HIV-1 p24 antigen determined by ELISA. In another set of experiments, Raji/DC-SIGN cells that were mixed with CBA-pre-exposed HIV and incubated for 60 minutes, were co-cultured with T lymphocyte C8166 cells after careful removal of the CBA and unattached virus particles from the supernatant. Virus transmission was recorded by quantifying syncytia formation after 24 to 48 hours post initiation of the co-cultures.

Results:  Virus capture by DC-SIGN⁺ cells was efficiently and dose-dependently inhibited by a variety of mannose-specific plant lectins, the mannose-specific procaryotic cyanovirin (CV-N), the GlcNAc-specific plant lectin (UDA), the mannose-specific non-peptidic antibiotic pradimicin A and the anti-gp120 monoclonal antibody 2G12, but not by the polyanions DS-5000, PRO-2000, and PVAS (sulfated polyvinyl alcohol). When DC-SIGN⁺ cells were exposed to drug-treated virus and after careful removal of drug and unbound virus, co-cultured with T lymphocyte C8166 cells, transmission of DC-SIGN-captured virus to C8166 cells (as measured by syncytia formation) was efficiently prevented by the CBA. All polyanions had a low, if any, inhibitory activity.

Conclusions:  CBA efficiently prevent HIV capture by DC-SIGN-expressing cells, and subsequent transmission to CD4⁺ T lymphocytes. In contrast, polyanions were markedly less efficient. These properties may be taken into consideration for microbicide drug development.