Inhibition of Endosome Tubulation with Phospholipase A2 Antagonists Prevents Transport of HIV‐1 across Mucosal Vaginal Epithelial Cells

Abstract

The mechanism by which HIV‐1 navigates the vaginal milieu en route to cause systemic infection is not fully understood. Vaginal epithelial cells are capable of taking up HIV‐1 and passing it along to HIV‐1 susceptible cells through trans‐infection. Trans‐infection is believed to occur in part through transcytosis which may utilize several different trafficking pathways. Data depicting the exact cellular pathway that the virus exploits to traverse vaginal epithelial cells remains incomplete. Our data shows that HIV‐1 enters vaginal epithelial cells through endocytosis which is interrupted by endocytic inhibitors. In addition, we demonstrate the intracellular trafficking pathway that HIV‐1 exploits to get across vaginal epithelial cells. After allowing equal amounts of HIV‐1 to enter vaginal cells; our data shows that reduction of endosome tubulation inhibited the release of HIV‐1. Inhibition of this pathway caused an accumulation of HIV‐1 within the cells. We also demonstrate that expression of the dominant negative Rab‐11 protein had a similar effect where HIV‐1 release from these cells was inhibited compared to our transfected control. We conclude that passage of HIV‐1 through vaginal epithelial cells is dependent on endosomal tubule formation and exploits the Rab‐11 dependent recycling pathway.Support provided by NIH/NHLBI 5T32HL007737–19 and NIH/NIGMS 1SC1GM089269