6533b7d0fe1ef96bd125a4a7
RESEARCH PRODUCT
Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.
Konstanze D. SchefferKonstantin H. MüllerRegina BrunnhöferLuise FlorinJef K. De BrabanderClaude P. MullerMartin E. MaierGilles A. Spodensubject
Vacuolar Proton-Translocating ATPasesEndosomeCell SurvivalCellBiologyAlphapapillomavirusEndocytosisInhibitory postsynaptic potentialAntiviral AgentsCell LineViral ProteinsmedicineHumansPharmacology (medical)Vacuolar ATPasePharmacologychemistry.chemical_classificationVacuolar Proton-Translocating ATPasesVirologyEndocytosisCell biologyInfectious Diseasesmedicine.anatomical_structureEnzymechemistryCell cultureHeLa Cellsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-05-01 | Antimicrobial agents and chemotherapy |