P40.05
Background: Understanding the precise mechanisms of HIV transmission across genital barriers is essential for studying vaccine development and inhibitory compounds. Previously, we illustrated that HIV can penetrate the intact female epithelium both ex vivo and in vivo, suggesting a diffusion mechanism for HIV entry; however, these studies were primarily focused on the lower female reproductive tract (FRT). We recently found that SIV based vectors can reach the ovary. The distance to transverse the uterus and fallopian tube of the upper FRT to reach the ovary is too far to reach by simple diffusion.
Methods: To investigate the possible role of cilia on the diffusion of HIV in the upper FRT, we examined the localization of cilia by staining for microtubules. Bundles of microtubules are present in the extended structure of individual cilia. To assess how ciliated epithelium might influence the movement of fluorescent beads and virus, we directly visualized the dynamics of fluorescent particles using time-lapse imaging.
Results: We find that the movement of cilia has a significant influence on the diffusion of virus and nanoparticles. First, the beating of the cilia accelerates and alters the diffusion of particles by causing convection currents in the regions adjacent to the ciliated epithelia. Second, the beating of the cilia pushes the particles away from the ciliated epithelium, essentially preventing particles from interacting directly with the underlying epithelial barrier.
Conclusions: These data reveal that the ciliated epithelium of the upper FRT provides protection from potential contacting particles. It seems likely that this action also drives an acceleration of the diffusion of the particles. The net effect of the lack of binding to the tissue and acceleration drives particles to traverse the long distance to the ovary. These data suggest that the anatomy of the FRT, combined with the action of cilia, must be taken into account to achieve complete protection by inhibitory modalities.
