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02114_1 EFFECTS OF CANDIDATE MICROBICIDES PRO2000 AND SAMMA ON DC-SIGN MEDIATED INFECTION OF CD4+ T-CELLS Klotman, Mary* Dendritic cell C-type lectins, including DC-SIGN, have been shown to bind to HIV-1 gp120 and play a role in virus transfer to T-cells. Dendritic cells expressing these molecules at mucosal surfaces may play a role in virus transmission. The candidate microbicides, SAMMA and Pro2000 both have been shown to block HIV-1 infection of susceptible CD4+ cells and to bind directly to HIV-1 gp120. We therefore tested the ability of these compounds to block either binding of HIV-1 to DC-SIGN or transfer of the virus from DC-SIGN expressing cells to susceptible T-cells. METHODS: DC-SIGN expressing THP-1(DC-THP-1) cells were incubated with HIV-1 in the presence or absence of microbicide. After washing, THP-1 cells were co-cultured with susceptible CD4+ T-cells in the presence of absence of the microbicide. Both DC-THP-1 cell and T-cell supernatants were monitored for HIV-1 infection by measuring p24 antigen. RESULTS: DC-THP-1 cells did not produce significant HIV-1 p24 in the presence or absence of microbicide. However, when the DC-THP-1 cells were then co-cultivated with activated T-cells, significant HIV-1 p24 was detected in the supernatants. Both Pro2000 and SAMMA blocked this production when the compounds were present at the time of the co-cultivation. However, neither compound blocked the successful transfer of the virus if only present during the initial infection of DC-THP-1 cells. CONCLUSIONS: The topical microbicides successfully blocked transfer of HIV-1 from DC-SIGN bearing cells to susceptible T-cells however; they did not appear to block the initial binding of the virus to the DC-bearing cell. Dr. Mary E. Klotman |
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