The effect of myricetin on HIV-1 infection using in vitro dual-chamber epithelial female genital tract model

The HIV infection by sexual transmission represents the predominant mode of infection in the world. The search for a natural compound that works as a microbicide becomes increasingly important. The Flavonoids, a group of phytochemicals, are normally found in plants and present pharmacological activities such as anti-inflammatory, anticancer and anti-HIV. The aim of this study was to evaluate the anti-HIV-1 activity of the flavonoid, Myricetin, in a Dual-Chamber Model of Epithelial Female Genital Tract. TZM-bl cells (1 × 10⁵) were seeded in the basal chamber (24 well plate), and HeLa cells were (1 × 10⁴) seeded on a transwell insert (8 µm pore). The HeLa cell layer confluence (Trans Epithelial Electric Resistance – TEER) was measured daily with a Millicell-ERS Volt-Ohm. On day 4 the optimal TEER (values higher than > 150 Ohm/cm²), was found; then 13µL (253 ng/mL – p24) of HIV-1BaL was added into each insert with Myricetin (50µM – 200µM). The controls used were 60µM of AZT – positive control, and Vehicle (DMSO 1%) – negative control. The cell viability and Luciferase assay were performed to analyze the cytotoxicity and inhibitory infection effect of Myricetin against HIV-1 BaL. The results obtained with the Dual-Chamber showed that the HIV-1 BaL can migrate through the HeLa cell layer and infect the TZM-bl (target cells). Myricetin crossed through the HeLa cells layer and had anti-HIV activity (> 85% infection inhibition (80 – 90µM)) and ≥90% of cell viability (50 – 100µM). In conclusion, Myricetin had anti-HIV activity. The Dual-Chamber provides a model that simulates the epithelial female genital tract to better understand the HIV pathogenicity and to study possible anti-HIV effects of new microbicide compounds.

Acknowledgement: Supported by NIH/NCCAM 5R00AT00650704