Inhibition by cellular vacuolar atpase impairs human papillomavirus uncoating and infection

Konstantin H. MÜller, Gilles A. Spoden, Konstanze D. Scheffer, Regina Brunnhöfer, Jef K. De Brabander, Martin E. Maier, Luise Florin, Claude P. Muller

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18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2905-2911
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume58
Issue number5
DOIs
StatePublished - May 2014

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

MÜller, K. H., Spoden, G. A., Scheffer, K. D., Brunnhöfer, R., De Brabander, J. K., Maier, M. E., Florin, L., & Muller, C. P. (2014). Inhibition by cellular vacuolar atpase impairs human papillomavirus uncoating and infection. Antimicrobial agents and chemotherapy, 58(5), 2905-2911. https://doi.org/10.1128/AAC.02284-13