Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.

  • Clinical and Applied Virology
May 01, 2014 By:
  • Muller KH
  • Spoden GA
  • Scheffer KD
  • Brunnhofer R
  • De Brabander JK
  • Maier ME
  • Florin L
  • Muller CP.

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.

2014 May. Antimicrob Agents Chemother.58(5):2905-11. Epub 2014 Mar 10.
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