Session 19bOral Abstract Presentations Microbicides Session Day and Time: Wednesday 12 - 12:30 pm Presentation Time: 12:00 Room: 302-306
104 Mannose-specific Lectins as Novel Microbicides against HIV? D. Schols1, S. Hatse*1, K. Vermeire1, K. Princen1, W. Peumans2, E. Van Damme3, E. De Clercq1, J. Balzarini1 1Rega Inst for Med Res, Katholieke Univ Leuven, Belgium; 2K U Leuven, Belgium; and 3Univ of Ghent, Belgium
Background: There is an urgent need for the development of effective microbicides against HIV. Here we evaluated the activity of several mannose-specific binding lectins for their antiviral activity against HIV-1, HIV-2, and drug-resistant HIV-1 strains.
Methods: Lectins were evaluated for their antiviral activity against a wide variety of HIV-1 and HIV-2 laboratory strains (R5, X4, R5/X4), primary clinical isolates and drug-resistant viruses in different T-cell lines, chemokine receptor-transfected cell lines, and PBMCs. Mitogenic activity and toxicity in several tumor cell lines and agglutinating activity were also examined. Flow cytometry, chemokine-induced Ca2 signaling, and HIV PCR entry assays were performed to decipher the mechanism of antiviral action.
Results: The lectins had no toxicity against any T-cell line (at concentrations up to 2 mg/ml), no agglutinating activity on human red blood cells (at 100 mg/ml) and no mitogenic effects in PBMCs (at 100 mg/ml). The lectins inhibited viral replication in all cell types examined with an EC50 varying from 0.1 to 0.8 mg/ml. They also prevented virus spread when cell cultures were exposed to persistently HIV-1 or HIV-2 infected T-cells. The lectins were additive or synergistic when evaluated in combination with any other known class of anti-HIV agents such as binding inhibitors (dextran sulfate), chemokines (SDF-1), chemokine receptor antagonists (AMD3100), fusion inhibitors (T-20), RT inhibitors (zidovudine, tenofovir), and protease inhibitors (amprenavir). The lectins did not interfere directly with the CD4 receptor or with the main HIV coreceptors CXCR4 or CCR5. Flow cytometry and HIV PCR entry assays indicated that the lectins acted at a post-CD4 binding step but prior to the onset of the RT-catalyzed transcription of RNA to viral DNA. The lectins were equally active against NRTI-, NNRTI-, and PI-resistant viruses.
Conclusions: Mannose-specific plant lectins proved markedly inhibitory to all HIV variants that were examined. They most likely interfere with viral entry. Their broad-spectrum anti-HIV activity makes them potential clinical candidates as anti-HIV microbicides to prevent the sexual transmission of AIDS.
