title: Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.
abstract: 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 anti-HPV activity can be provided.
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg.
authors.forename: Konstantin H
authors.initials: KH
authors.lastname: Müller
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Spoden
authors.forename: Konstanze D
authors.initials: KD
authors.lastname: Scheffer
authors.forename: Regina
authors.initials: R
authors.lastname: Brunnhöfer
authors.forename: Jef K
authors.initials: JK
authors.lastname: De Brabander
authors.forename: Martin E
authors.initials: ME
authors.lastname: Maier
authors.forename: Luise
authors.initials: L
authors.lastname: Florin
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D052685:Alphapapillomavirus / Q000187:drug effects* / Q000472:pathogenicity; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D025262:Vacuolar Proton-Translocating ATPases