Inhibition by Cellular Vacuolar ATPase Impairs Human Papillomavirus Uncoating and Infection

Several viruses, including human papillomaviruses, depend on endosomal acidification for successful infection. Hence, the multisubunit enzyme vacuolar ATPase (V- ATPase), which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. In the present study, we show that V- ATPase is required for human papillomavirus (HPV) infection and that uncoating/ disassembly but not endocytosis is affected by V- ATPase inhibition. The infection inhibitory potencies of saliphenylhalamide, a proven V- ATPase inhibitor, and its derivatives, as well as those of other V- ATPase inhibitors, were analyzed on different HPV types in relevant cell lines. Variation in the selectivity indices among V- ATPase inhibitors was high, while variation for the same inhibitor against different HPV subtypes was low, indicating that broad- spectrum antiHPV activity can be provided.