Transcytosis as a Mechanism of HIV-1 Entry into Columnar Epithelial Explants of the Female Reproductive Tract

During male-to-female transmission, HIV-1 must cross the mucosal epithelium of the female reproductive tract to gain access to underlying target cells. Previously, we demonstrated that HIV-1 can penetrate intact columnar and squamous genital epithelia in both <i>ex vivo</i> and <i>in vivo</i> systems. We found that the virus enters the squamous epithelium via a diffusion-based mechanism, but the mechanism of entry in columnar epithelium remained elusive. Using a similar set of approaches, we now demonstrate that HIV enters the endocervical simple columnar epithelium via endocytosis. By exposing human endocervical explant tissue to small molecule endocytosis inhibitors prior to virus exposure, we show that virus penetration into the simple columnar barrier is impeded. These data suggest a transcytosis-based mechanism for HIV-1 penetration into the endocervical columnar barrier.